• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5941-5948
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• 2013

Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4409-4419
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• 2015

The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MIC-affected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showed relatively higher BNMN and MNL (P<0.05) in the MIC-affected than in the controls. Exposed females (EF) exhibited significantly higher BNMN and MNL (P<0.01) than their unexposed counterparts. Similarly, female offspring of the exposed (FOE) also suffered higher BNMN and MNL (P<0.05) than in controls. A significant reduction in NDI (P<0.05) was found only in EF. The affected group of non-smokers and non-alcoholics featured a higher frequency of BNMN and MNL than the control group of non-smokers and non-alcoholics (P<0.01). Similarly, the affected group of tobacco chewers showed significantly higher BNMN and MNL (P<0.001) than the non-chewers. Amongst the affected, smoking and alcohol consumption were not associated with statistically significant differences in BNMN, MNL and NDI. Nevertheless, tobacco-chewing had a preponderant effect with respect to MNL. A reasonable correlation between MNL and lifestyle habits (smoking, alcohol consumption and tobacco-chewing) was observed only in the controls. Our results suggest that EF and FOE are more susceptible to cancer development, as compared to EM and MOE. The genotoxic outcome detected in FOE reflects their parental exposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute to cancer risk, especially in the EF and FOE.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2003.10a
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• pp.121-121
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• 2003

• Toxicological Research
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• v.7 no.1
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• pp.83-92
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• 1991

Complexities of testis structure and function are emphasized in morphometrical and genotoxic evaluation by statistical analysis. F-344 rats were treated with azinphos methyl, cyclophosphomide, and dichlorvos. And Brdu was injected with intrapertionially before sacrifice. The existence and degree of DNA damage were measured by Brdu labeling index which represented relative amount of Brdu incorporated in DNA, morphometric change was evaluated by the relative length of tubular diameter in circular seminiferous tubules and the number of spermatogonia per Sertoli cell in stage IX seminiferous tubules.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.73-73
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• 2004

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.84-84
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.121-121
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• 2003

Cricket (Gryllus bimacutus) is mass-bred in 6 cycles per one year in insect farms. They are used as dry or live foods for animals, tropical fish, reptile and amphibians. Therefore, it is necessary to study the genotoxicity of whole bodies of G. bimaculatus.(omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.165.1-165.1
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• 2003

This research was designed to examine the presence of mutagenic/carcinogenic compounds in airborne pollutants in diesel particulate matter using an integrated biological approach. Respirable air borne particulate matter (PM2.5: <2.5mm) was collected from diesel engine exhaust using a high-volume sampler equipped with a cascade impactor. (omitted)

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.45-45
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• 2001

Heterocyclic aromatic amines (HCAs) are established genotoxic human cancer risks, that display their activity also in a number of animal models and in vitro. They are formed during the trying or broiling of creatinine-containing foods, mainly fish or meat. We established that mixing soy protein with ground meat blocks the formation of HCAs. we also observed that coating the surface of meat with polyphenols green or from black tea gives a dose - related reduction of the formation of HCAs.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2487-2490
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• 2013

In Thai traditional medicine, Plumbago indica or Jetamul-Pleung-Dang in Thai is known to have health benefit especially for anti-inflammatory, antibacterial, and antitumor activities. However, the mechanisms of its action are still uncertain. One of which might be genotoxic effects. In the present study, we investigated the genotoxicity of an ethanolic extract of Plumbago indica root (EEPIR) by sister chromatid exchange (SCE) assay in human lymphocytes. Results have shown that all treatments with EEPIR ($12.5-100{\mu}g/ml$) could induce cell cycle delay as shown by significant increase in the number of metaphase cells in the first cell cycle but neither in the second nor the third cell cycle. Only at concentrations of 25, 50, and $100{\mu}g/ml$ were SCE levels significantly increased above that of the control (p<0.05). EEPIR at a concentration of $500{\mu}g/ml$ induced cell death as few mitotic cells were shown. Accordingly, EEPIR ($25-100{\mu}g/ml$) is genotoxic in human lymphocytes and cytotoxic at concentrations of ${\geq}500{\mu}g/ml$ in vitro. Therefore, these activities of the EEPIR could serve its potential therapeutic effects, especially as an anticancer agent. Further study of EEPIR in vivo is now needed to support this in vitro evidence.