Papers by Rupa Doppalapudi
Environmental Research, 1989
We analyzed the frequency of chromosomal aberrations in peripheral lymphocytes from underground m... more We analyzed the frequency of chromosomal aberrations in peripheral lymphocytes from underground miners from the Casapalca (n = 8, mean age = 45 y, range = 36 y to 55 y) and Bellavista (n = 8, mean age = 28 y, range 23 y to 34 y) high-altitude mining camps in the Peruvian Andes. This population was occupationally exposed to heavy metals such as lead and zinc as well as diesel emission particles, organic solvents and mine dust. The control groups consisted of individuals from a high altitude farming community in the Peruvian village of Tinco (n = 8, mean age = 37 y, range = 25 y to 52 y) and the sea level city of Lima (n = 14, mean age = 26 y, range = 20 y to 35 y). All individuals were male native Peruvians. A significantly higher incidence (1.88%, p < 0.05) of chromosomal aberrations (chromatid deletions and breaks, chromosome breaks and acentric fragments) were detected in lymphocytes from miners at the Casapalca camp as compared to miners from the Bellavista camp (0.5%, chromatid deletions and acentric fragments only) and the Lima sea level (0.07%, chromatid deletions only) and Tinco high altitude (no aberrations) controls. These results suggest that male native Peruvians occupationally exposed to underground mining activity have an increased frequency of chromosomal aberrations, which could be related to both age and exposure time. The increased chromosomal damage observed in the mining populations studied may be attributable to the complex mixture of genotoxic agents to which the miners may have been exposed.
A novel multicolor fluorescence in situ hybridization approach, using an a satellite probe which ... more A novel multicolor fluorescence in situ hybridization approach, using an a satellite probe which labels the centromeric region on chromosome 1 and a classical satellite probe which targets an adjacent breakage-prone region (Iql2), has been used to detect both hyperdiploidy and chromo some breakage in interphase human cells. With the use of this technique significant increases in chromosomal breakage were
Journal of Radiation Research
Cancer research, 1994
Benzene is a widely recognized human and animal carcinogen. In spite of considerable research, re... more Benzene is a widely recognized human and animal carcinogen. In spite of considerable research, relatively little is known about the genotoxic events that accompany benzene exposure in vivo. To gain insights into the mechanisms underlying the genotoxic effects of benzene, we have characterized the origin of the micronuclei that are formed in bone marrow erythrocytes and splenic lymphocytes of benzene-treated mice using two molecular cytogenetic approaches: (a) fluorescence in situ hybridization with a centromeric DNA probe; and (b) staining with the calcinosis-Raynaud's phenomenon-esophageal dismobility-sclerodactyly-telangiectasia syndrome of scleroderma (CREST) antibody, an antibody recognizing a centromeric protein. Following the p.o. administration of benzene (220 or 440 mg/kg) to male CD-1 mice, a significant increase in micronuclei was observed in the bone marrow erythrocytes. In situ hybridization with a centromeric DNA probe and immunofluorescent staining with the CREST a...
Cancer research, 1995
A novel multicolor fluorescence in situ hybridization approach, using an alpha satellite probe wh... more A novel multicolor fluorescence in situ hybridization approach, using an alpha satellite probe which labels the centromeric region on chromosome 1 and a classical satellite probe which targets an adjacent breakage-prone region (1q12), has been used to detect both hyperdiploidy and chromosome breakage in interphase human cells. With the use of this technique significant increases in chromosomal breakage were observed in interphase and metaphase lymphocytes irradiated in vitro. Metaphase analysis indicated that a significant proportion of these breakage events represented potentially stable aberrations such as translocations and inversions. A comparison of frequencies using a single classical satellite probe and the adjacent alpha and classical satellite probes indicated that this tandem label procedure allowed chromosomal breakage to be detected and distinguished from hyperdiploidy in untreated interphase lymphocytes, indicating the potential of this procedure for human biomonitoring...
International journal of toxicology, Jan 20, 2015
A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epidid... more A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminar...
Research report (Health Effects Institute), 2003
This study was conducted to validate biomarkers for early detection of benzene exposure and effec... more This study was conducted to validate biomarkers for early detection of benzene exposure and effect in 2 phases. The main purpose of phase 1 was to determine whether these biomarkers could reliably detect differences between workers with high exposure levels and unexposed subjects, which is the minimal screening criterion for a biomarker assay. Phase 2 of the study mainly focused on evaluating the exposure-response relation, confounding factors, and sensitivities of biomarkers for low benzene exposures. The Chinese occupational population studied had a broad range of benzene exposures. On the day of biological sample collection, exposures ranged from 0.06 to 122 ppm with a median exposure of 3.2 ppm. The median of the 4-week mean benzene exposures was 3.8 ppm, and the median lifetime cumulative exposure was 51.1 ppm-years. Compared with benzene levels in collected samples, toluene levels were relatively high, with a median of 12.6 ppm (mean, 26.3 ppm), but xylene levels were low, wit...
Mutation Research/genetic Toxicology, 1994
Radiation Research, 2013
Two hydroxypyridinone-containing actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3... more Two hydroxypyridinone-containing actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), are being developed for the treatment of internal actinide contamination by chelation therapy. Dose-response efficacy profiles in mice were established for the removal of intravenously injected (238)Pu and (241)Am after parenteral and oral treatment with these chelators. In both cases, presumed efficacious doses promoted substantially greater actinide elimination rates than the currently approved agent, diethylenetriamine-pentaacetic acid, considering two different interspecies scaling methods for the conversion of human doses to equivalent rodent dose levels. In addition, genotoxicity of both ligands was assessed using the Salmonella/ Escherichia coli /microsome plate incorporation test and the Chinese hamster ovary cell chromosome aberration assay, showing that neither ligand is genotoxic, in the presence and absence of metabolic activation. Finally, maximum tolerated dose studies were performed in rats for seven consecutive daily oral administrations with the chelators, confirming the safety of the presumed efficacious doses for 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). The results of these studies add to the growing body of evidence that both decorporation agents have remarkable decorporation efficacy properties and promising safety toxicology profiles. These results are necessary components of the regulatory approval process and will help determine the optimal human dosing regimens for the treatment of internal radionuclide contamination.
Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2012
The genotoxic activities of three cancer chemopreventive drug candidates, CP-31398 (a cell permea... more The genotoxic activities of three cancer chemopreventive drug candidates, CP-31398 (a cell permeable styrylquinazoline p53 modulator), SHetA2 (a flexible heteroarotinoid), and phospho-ibuprofen (PI, a derivative of ibuprofen) were tested. None of the compounds were mutagenic in the Salmonella/Escherichia coli/microsome plate incorporation test. CP-31398 and SHetA2 did not induce chromosomal aberrations (CA) in Chinese hamster ovary (CHO) cells, either in the presence or absence of rat hepatic S9 (S9). PI induced CA in CHO cells, but only in the presence of S9. PI, its parent compound ibuprofen, and its moiety diethoxyphosphoryloxybutyl alcohol (DEPBA) were tested for CA and micronuclei (MN) in CHO cells in the presence of S9. PI induced CA as well as MN, both kinetochore-positive (Kin+) and -negative (Kin-), in the presence of S9 at ≤100μg/ml. Ibuprofen was negative for CA, positive for MN with Kin+ at 250μg/ml, and positive for MN with Kin- at 125 and 250μg/ml. DEPBA induced neither CA nor MN at ≤5000μg/ml. The induction of chromosomal damage in PI-treated CHO cells in the presence of S9 may be due to its metabolites. None of the compounds were genotoxic, in the presence or absence of S9, in the GADD45α-GFP Human GreenScreen assay and none induced MN in mouse bone marrow erythrocytes.
Food and Chemical Toxicology, 1991
Mutation Research Letters, 1995
Human genetics, 1989
Chromosomal aberrations, sister chromatid exchanges, mitotic index and cell kinetics were observe... more Chromosomal aberrations, sister chromatid exchanges, mitotic index and cell kinetics were observed in human peripheral lymphocytes after treatment with four different concentrations (0.0125, 0.025, 0.05 and 0.1 microgram/ml) of benzene hexachloride (BHC), an organochlorine pesticide. Cells were treated with BHC for 24, 48 and 72 h. There was a dose-dependent increase in the frequency of chromosomal aberrations and sister chromatid exchanges. A significant decrease in mitotic index was observed at all concentrations and times of exposure. BHC did not show a significant effect on cell kinetics.
Bulletin of environmental …, 1988
... In vitro Effect of Monocrotophos on Human Lymphocytes DS Rupa, PV Lakshman Rao, PP Reddy, and... more ... In vitro Effect of Monocrotophos on Human Lymphocytes DS Rupa, PV Lakshman Rao, PP Reddy, and OS Reddi Institute of Genetics, Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad--500 016 Andhra Pradesh, India ...
…, 2002
o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be ... more o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA. Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variable results. This difference has been attributed to the presence of the sodium salt. To determine cellular and genetic alterations in the rat bladder and the influence of the sodium salt, F344 rats were administered 2% OPP, 2% NaCl and 2% NaCl ⍣ 2% OPP in their diet for 14 days. Twenty-four hours before being killed the animals were administered 5-bromo-2Ј-deoxyuridine (BrdU) by i.p. injection. Bladder cells were isolated, stained with DAPI and scored for the presence of micronuclei and incorporation of BrdU into replicating cells. To determine changes in chromosome number, we used fluorescence in situ hybridization (FISH) with a DNA probe for rat chromosome 4. Significant increases in the frequency of micronuclei and BrdU incorporation were seen in bladder cells of rats from all treatment groups. In contrast, the frequency of hyperdiploidy/polyploidy in treated animals was not increased over that seen in controls. A high control frequency of cells with three or more hybridization signals was seen, probably due to the presence of polyploid cells in the bladder. The presence of polyploid cells combined with cytotoxicity and compensatory cell proliferation makes it difficult to determine whether OPP is capable of inducing aneuploidy in the rat urothelium. In summary, these studies show that OPP can cause cellular and chromosomal alterations in rat bladder cells in the absence of the sodium salt. These results also indicate that at high concentrations the sodium salt can enhance chromosomal damage in the rat urothelium.
Compounds bactericidal against both replicating and non-replicating Mtb may shorten the length of... more Compounds bactericidal against both replicating and non-replicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and non-replicating Mtb. Medicinal chemistry optimization, guided by semi-empirical molecular orbital calculations, identified a new lead compound (27q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC(50)) against Vero cells of 25 μg/mL. 27q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 27q was also negative in a L5178Y MOLY assay, indicating low potential for genetic-toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.
Genetics and Molecular …, 2007
Mutation Research/Genetic Toxicology, 1989
Carcinogenesis, 1997
Epidemiological studies have shown that a high incidence of oral cancers is associated with chewi... more Epidemiological studies have shown that a high incidence of oral cancers is associated with chewing betel quid. Since chromosomal aberrations are involved in many types of cancers, we investigated whether increased frequencies of chromosomal alterations could be detected in the oral mucosa cells of betel quid chewers as compared to nonchewers. Due to the difficulty in culturing these epithelial cells, we used multicolor FISH with adjacent DNA probes to detect hyperdiploidy and breakage/exchanges affecting the 1cen-q12 region in interphase cells. Buccal mucosa cells from 19 male betel quid chewers and 23 non-chewers were hybridized and 1000 cells per donor were evaluated. A highly significant increase in the frequency of breakage affecting 1cen-1q12 region was observed in the mucosa cells of the chewers as compared to the non-chewers. A good correlation was also seen between breakage and duration of chewing. A modest increase in hyperdiploidy for chromosome 1 was also observed among chewers who had used betel quid for many years. These results indicate that this FISH approach can be useful for human biomonitoring, particularly for detecting alterations in nondividing cells.
Environmental and Molecular Mutagenesis, 2006
Abstract The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity T... more Abstract The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Testing (IWGT), comprised of experts from Japan, Europe, and the United States, met on August 29, 2003, in Aberdeen, Scotland, United Kingdom. This meeting of ...
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Papers by Rupa Doppalapudi