apsule'': The potential as well as some limitations of semipermeable membrane devices in monitori... more apsule'': The potential as well as some limitations of semipermeable membrane devices in monitoring the biological eects of organic pollutants has been demonstrated.
Sister chromatid exchanges (SCEs) were analysed in lymphocytes from 12 control persons and 33 Che... more Sister chromatid exchanges (SCEs) were analysed in lymphocytes from 12 control persons and 33 Chernobyl clean-up workers. The group of Chernobyl clean-up workers consisted of civilians who were forced to go to Chernobyl to clean up environmental contamination caused by Chernobyl disaster. On average, they received 0.13 (range 0.04-0.249) Gy of external irradiation before returning to home. Cytogenetic analyses were performed 6-8 years after the irradiation. Standard cytogenetic techniques were used. Mean SCE frequency was 7.45 +/- 0.69 SCE/cell in controls and 10.30 +/- 0.31 SCE/cell in clean-up workers (p < 0.05). Analysis of variance showed that exposure to radiation explained 19.6%, occupational exposure to various chemical substances, 11.9%, coffee consumption, 8.3%, smoking, 4.2%, interaction between smoking and coffee consumption, 3.6%, and alcohol abuse, 3.4% of total variation in SCE frequency. Effects of all above confounding factors were significant (p < 0.05). In ad...
Patients with prostate cancer who have biochemical recurrence after curative therapy are at highe... more Patients with prostate cancer who have biochemical recurrence after curative therapy are at higher risk for distant metastasis and cancer specific death. Assessment of aberrant DNA methylation in urine might complement currently used clinical prognostic factors and serve as a noninvasive tool for early prediction of biochemical recurrence after radical prostatectomy. Promoter methylation of 7 genes was evaluated by methylation sensitive polymerase chain reaction in 149 prostate cancer tissues, 37 noncancerous prostate tissues and 17 benign prostatic hyperplasia samples. Quantitative polymerase chain reaction was used for DNA methylation analysis of the urine of 253 patients with prostate cancer and 32 with benign prostatic hyperplasia. In prostate cancer tissue the most frequently methylated genes were RASSF1, GSTP1 and RARB, which combined were positively identified in 85% of cases. These genes were also methylated in the urine of 60% of patients with prostate cancer. RASSF1 was methylated in 45% of prostate cancer urine samples with methylation intensity significantly higher in prostate cancer than in benign prostatic hyperplasia cases (p = 0.018). In a univariate model RASSF1 methylation and the total number of methylated genes in prostate cancer tissue were predictive of time to biochemical recurrence (p = 0.019 and 0.043, respectively). On multivariate analysis RASSF1 methylation together with pathological stage was the most significant predictor of biochemical recurrence in patients with Gleason score 6 tumors when analyzed in tissue and urine (p ≤0.001). Hypermethylation of RASSF1 in cancerous tissue and urine from patients with prostate cancer correlated with biochemical recurrence after radical prostatectomy. The prognostic potential of this biomarker deserves further investigation.
The objective of this study was to determine whether nitrofurantoin, used for long-term antimicro... more The objective of this study was to determine whether nitrofurantoin, used for long-term antimicrobial prophylaxis of urinary tract infection, may induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in lymphocytes of treated children. Ninety-nine blood samples were taken from 69 children aged from 0.2 to 13 years and suffering from urinary tract infection. The treatment consisted of oral administration of nitrofurantoin at doses of 5-8 mg/kg/day for the first 7 days and at doses of 1-2 mg/kg/day for the rest of the treatment period. Blood was sampled before the start of the nitrofurantoin therapy and after 1, 3, 6 and 12 months of the therapy. Analysis of variance showed no statistically significant increase in CA and SCE frequencies in lymphocytes of children treated with nitrofurantoin for 1-12 months. However, a significant increase in SCE rates was determined in lymphocytes of those patients whose blood samples were available both before and after treatment with nitrofurantoin (6.21 ⍨ 0.28 and 7.30 ⍨ 0.39 SCE/cell, respectively, P ⍧ 0.0315, Student's paired t-test). Moreover, there was a statistically significant correlation (r ⍧ 0.6603, P ⍧ 0.0270) between cumulative dose of nitrofurantoin and SCE frequency in lymphocytes of children after 1 month of the therapy. Also, in vitro experiments indicated that nitrofurantoin was able to induce both CAs and SCEs in human lymphocytes. Positive findings with chromosome aberrations and SCEs in vitro and suggestive results with SCEs in vivo indicate that further, much larger follow-up studies are needed to elucidate the genetic safety of the therapeutic use of nitrofurantoin.
Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is t... more Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is the most common gene fusion in PCa, whereas activation of telomerase is a common feature of various malignancies. The aim of our study was to explore the combined utility of these and some other biomarkers in predicting biochemical recurrence after radical prostatectomy. Prostate specimens and urine sediments from 179 previously untreated patients with pT2-pT3 stage PCa were analyzed for expression of telomerase (TERT and TR) and the TMPRSS2-ERG fusion gene by means of reverse transcription PCR. Real-time PCR was used for quantification of ERG and SPINK1 expression. In total, 74% (117/158) of the prostate adenocarcinomas were positive for the TMPRSS2-ERG and/or TERT expression. Noninvasively, these transcripts were identified in 31% (19/61) of catheterized urine specimens. Significantly higher expression of ERG was detected in TMPRSS2-ERG-positive tumors (P < 0.0001), whereas more intense expression of SPINK1 was characteristic for the TMPRSS2-ERGnegative tumors (P ¼ 0.003). TERT-positive cases also had elevated levels of ERG (P ¼ 0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors. The cases negative for both transcripts, TMPRSS2-ERG and TERT, rarely recurred (P ¼ 0.014) and showed significantly longer biochemical recurrence-free period (P ¼ 0.022) as compared to the TMPRSS2-ERG and/or TERT-positive cases. The results of our study suggest that combined analysis of TMPRSS2-ERG and TERT expression can be a valuable tool for early prediction of biochemical recurrence of PCa after radical prostatectomy.
Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and s... more Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Men-thaÂpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test. #
were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and ... more were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and in gill cells of blue mussels (Mytilus edulis). The organisms were collected from three study stations in the Baltic Sea and from seven stations in the North Sea (Karmsund area, Norway) 4 times. The statistically significant differences obtained were related to the season, sex of the fish, and sampling locality. Higher MN frequencies were found in fish and mussels collected from the most polluted study stations in the North Sea. The same tendency could be described in the Baltic Sea; however, it was masked by the recent oil spill from the Butinge oil terminal. Our results showing higher MN frequencies in presumably what were the most polluted study locations suggest that MN tests in fish and mussels may be used for the detection of genotoxic effects in a marine environment. The endpoint is well characterized and can be easily recognized, and the technique is convenient to use in field samplings following standard procedures and protocols.
Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recen... more Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies which associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22,358 cancer free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium (RR = 1.31; 95% confidence interval (CI) 1.07-1.60) and in the high (RR = 1.41; 95% CI 1.16-1.72) tertiles, when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI= 1.34-3.68). The strongest association was found for stomach cancer (RR medium =1.17 (95% CI= 0.37-3.70); RR high =3.13 (95% CI= 1.17-8.39)). Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.
Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostat... more Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostatic drug phopurinum in uioo and in oitro were studied in human lymphocytes. Phopurinum was found to cause a significant increase of CAs in lymphocytes of patients undergoing cytostatic therapy. Increased CA rates, however, declined rapidly after the cessation of treatment.
A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of... more A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations (chromosome type and chromatid type) are limited. A total of 6,430 healthy individuals from nine laboratories in Croatia, Hungary, Lithuania, Poland, and Slovakia, included in chromosomal aberration surveys performed during 1978-2002, were followed up for cancer incidence or mortality for an average of 8.5 years; 200 cancer cases were observed. Compared with that for the low-tertile level of chromosomal aberrations, the relative risks of cancer for the medium and high tertiles were 1.78 (95% confidence interval: 1.19, 2.67) and 1.81 (95% confidence interval: 1.20, 2.73), respectively. The relative risk for chromosome-type aberrations above versus below the median was 1.50 (95% confidence interval: 1.12, 2.01), while that for chromatid-type aberrations was 0.97 (95% confidence interval: 0.72, 1.31). The analyses of risk of specific cancers were limited by small numbers, but the association was stronger for stomach cancer. This study confirms the previously reported association between level of chromosomal aberrations and cancer risk and provides novel information on the type of aberrations more strongly predictive of cancer risk and on the types of cancer more strongly predicted by chromosomal aberrations.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2006
Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of s... more Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
apsule'': The potential as well as some limitations of semipermeable membrane devices in monitori... more apsule'': The potential as well as some limitations of semipermeable membrane devices in monitoring the biological eects of organic pollutants has been demonstrated.
Sister chromatid exchanges (SCEs) were analysed in lymphocytes from 12 control persons and 33 Che... more Sister chromatid exchanges (SCEs) were analysed in lymphocytes from 12 control persons and 33 Chernobyl clean-up workers. The group of Chernobyl clean-up workers consisted of civilians who were forced to go to Chernobyl to clean up environmental contamination caused by Chernobyl disaster. On average, they received 0.13 (range 0.04-0.249) Gy of external irradiation before returning to home. Cytogenetic analyses were performed 6-8 years after the irradiation. Standard cytogenetic techniques were used. Mean SCE frequency was 7.45 +/- 0.69 SCE/cell in controls and 10.30 +/- 0.31 SCE/cell in clean-up workers (p < 0.05). Analysis of variance showed that exposure to radiation explained 19.6%, occupational exposure to various chemical substances, 11.9%, coffee consumption, 8.3%, smoking, 4.2%, interaction between smoking and coffee consumption, 3.6%, and alcohol abuse, 3.4% of total variation in SCE frequency. Effects of all above confounding factors were significant (p < 0.05). In ad...
Patients with prostate cancer who have biochemical recurrence after curative therapy are at highe... more Patients with prostate cancer who have biochemical recurrence after curative therapy are at higher risk for distant metastasis and cancer specific death. Assessment of aberrant DNA methylation in urine might complement currently used clinical prognostic factors and serve as a noninvasive tool for early prediction of biochemical recurrence after radical prostatectomy. Promoter methylation of 7 genes was evaluated by methylation sensitive polymerase chain reaction in 149 prostate cancer tissues, 37 noncancerous prostate tissues and 17 benign prostatic hyperplasia samples. Quantitative polymerase chain reaction was used for DNA methylation analysis of the urine of 253 patients with prostate cancer and 32 with benign prostatic hyperplasia. In prostate cancer tissue the most frequently methylated genes were RASSF1, GSTP1 and RARB, which combined were positively identified in 85% of cases. These genes were also methylated in the urine of 60% of patients with prostate cancer. RASSF1 was methylated in 45% of prostate cancer urine samples with methylation intensity significantly higher in prostate cancer than in benign prostatic hyperplasia cases (p = 0.018). In a univariate model RASSF1 methylation and the total number of methylated genes in prostate cancer tissue were predictive of time to biochemical recurrence (p = 0.019 and 0.043, respectively). On multivariate analysis RASSF1 methylation together with pathological stage was the most significant predictor of biochemical recurrence in patients with Gleason score 6 tumors when analyzed in tissue and urine (p ≤0.001). Hypermethylation of RASSF1 in cancerous tissue and urine from patients with prostate cancer correlated with biochemical recurrence after radical prostatectomy. The prognostic potential of this biomarker deserves further investigation.
The objective of this study was to determine whether nitrofurantoin, used for long-term antimicro... more The objective of this study was to determine whether nitrofurantoin, used for long-term antimicrobial prophylaxis of urinary tract infection, may induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in lymphocytes of treated children. Ninety-nine blood samples were taken from 69 children aged from 0.2 to 13 years and suffering from urinary tract infection. The treatment consisted of oral administration of nitrofurantoin at doses of 5-8 mg/kg/day for the first 7 days and at doses of 1-2 mg/kg/day for the rest of the treatment period. Blood was sampled before the start of the nitrofurantoin therapy and after 1, 3, 6 and 12 months of the therapy. Analysis of variance showed no statistically significant increase in CA and SCE frequencies in lymphocytes of children treated with nitrofurantoin for 1-12 months. However, a significant increase in SCE rates was determined in lymphocytes of those patients whose blood samples were available both before and after treatment with nitrofurantoin (6.21 ⍨ 0.28 and 7.30 ⍨ 0.39 SCE/cell, respectively, P ⍧ 0.0315, Student's paired t-test). Moreover, there was a statistically significant correlation (r ⍧ 0.6603, P ⍧ 0.0270) between cumulative dose of nitrofurantoin and SCE frequency in lymphocytes of children after 1 month of the therapy. Also, in vitro experiments indicated that nitrofurantoin was able to induce both CAs and SCEs in human lymphocytes. Positive findings with chromosome aberrations and SCEs in vitro and suggestive results with SCEs in vivo indicate that further, much larger follow-up studies are needed to elucidate the genetic safety of the therapeutic use of nitrofurantoin.
Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is t... more Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is the most common gene fusion in PCa, whereas activation of telomerase is a common feature of various malignancies. The aim of our study was to explore the combined utility of these and some other biomarkers in predicting biochemical recurrence after radical prostatectomy. Prostate specimens and urine sediments from 179 previously untreated patients with pT2-pT3 stage PCa were analyzed for expression of telomerase (TERT and TR) and the TMPRSS2-ERG fusion gene by means of reverse transcription PCR. Real-time PCR was used for quantification of ERG and SPINK1 expression. In total, 74% (117/158) of the prostate adenocarcinomas were positive for the TMPRSS2-ERG and/or TERT expression. Noninvasively, these transcripts were identified in 31% (19/61) of catheterized urine specimens. Significantly higher expression of ERG was detected in TMPRSS2-ERG-positive tumors (P < 0.0001), whereas more intense expression of SPINK1 was characteristic for the TMPRSS2-ERGnegative tumors (P ¼ 0.003). TERT-positive cases also had elevated levels of ERG (P ¼ 0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors. The cases negative for both transcripts, TMPRSS2-ERG and TERT, rarely recurred (P ¼ 0.014) and showed significantly longer biochemical recurrence-free period (P ¼ 0.022) as compared to the TMPRSS2-ERG and/or TERT-positive cases. The results of our study suggest that combined analysis of TMPRSS2-ERG and TERT expression can be a valuable tool for early prediction of biochemical recurrence of PCa after radical prostatectomy.
Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and s... more Genotoxic properties of the essential oils extracted from dill (Anethum graveolens L.) herb and seeds, peppermint (Men-thaÂpiperita L.) herb and pine (Pinus sylvestris L.) needles were studied using chromosome aberration (CA) and sister chromatid exchange (SCE) tests in human lymphocytes in vitro, and Drosophila melanogaster somatic mutation and recombination test (SMART) in vivo. In the CA test, the most active essential oil was from dill seeds, then followed essential oils from dill herb, peppermint herb and pine needles, respectively. In the SCE test, the most active essential oils were from dill herb and seeds followed by essential oils from pine needles and peppermint herb. Essential oils from dill herb and seeds and pine needles induced CA and SCE in a clear dose-dependent manner, while peppermint essential oil induced SCE in a dose-independent manner. All essential oils were cytotoxic for human lymphocytes. In the SMART test, a dose-dependent increase in mutation frequency was observed for essential oils from pine and dill herb. Peppermint essential oil induced mutations in a dose-independent manner. Essential oil from dill seeds was almost inactive in the SMART test. #
were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and ... more were analyzed in erythrocytes of flounder (Platichthys flesus) and wrasse (Symphodus melops) and in gill cells of blue mussels (Mytilus edulis). The organisms were collected from three study stations in the Baltic Sea and from seven stations in the North Sea (Karmsund area, Norway) 4 times. The statistically significant differences obtained were related to the season, sex of the fish, and sampling locality. Higher MN frequencies were found in fish and mussels collected from the most polluted study stations in the North Sea. The same tendency could be described in the Baltic Sea; however, it was masked by the recent oil spill from the Butinge oil terminal. Our results showing higher MN frequencies in presumably what were the most polluted study locations suggest that MN tests in fish and mussels may be used for the detection of genotoxic effects in a marine environment. The endpoint is well characterized and can be easily recognized, and the technique is convenient to use in field samplings following standard procedures and protocols.
Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recen... more Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies which associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22,358 cancer free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965-2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium (RR = 1.31; 95% confidence interval (CI) 1.07-1.60) and in the high (RR = 1.41; 95% CI 1.16-1.72) tertiles, when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI= 1.34-3.68). The strongest association was found for stomach cancer (RR medium =1.17 (95% CI= 0.37-3.70); RR high =3.13 (95% CI= 1.17-8.39)). Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type.
Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostat... more Sister chromatid exchanges (SCEs) and structural chromosome aberrations (CAs) induced by cytostatic drug phopurinum in uioo and in oitro were studied in human lymphocytes. Phopurinum was found to cause a significant increase of CAs in lymphocytes of patients undergoing cytostatic therapy. Increased CA rates, however, declined rapidly after the cessation of treatment.
A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of... more A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations (chromosome type and chromatid type) are limited. A total of 6,430 healthy individuals from nine laboratories in Croatia, Hungary, Lithuania, Poland, and Slovakia, included in chromosomal aberration surveys performed during 1978-2002, were followed up for cancer incidence or mortality for an average of 8.5 years; 200 cancer cases were observed. Compared with that for the low-tertile level of chromosomal aberrations, the relative risks of cancer for the medium and high tertiles were 1.78 (95% confidence interval: 1.19, 2.67) and 1.81 (95% confidence interval: 1.20, 2.73), respectively. The relative risk for chromosome-type aberrations above versus below the median was 1.50 (95% confidence interval: 1.12, 2.01), while that for chromatid-type aberrations was 0.97 (95% confidence interval: 0.72, 1.31). The analyses of risk of specific cancers were limited by small numbers, but the association was stronger for stomach cancer. This study confirms the previously reported association between level of chromosomal aberrations and cancer risk and provides novel information on the type of aberrations more strongly predictive of cancer risk and on the types of cancer more strongly predicted by chromosomal aberrations.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2006
Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of s... more Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.
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Papers by Juozas Lazutka