Genotoxic agents

Cavalieri, E. Frenkel, K. Liehr, J. G. Rogan, E. Roy, D. Estrogens as endogenous genotoxic agents—DNA adducts and mutations. J. Natl. Cancer Inst. Monogr. 2000, 27, 75-93. 

Nitro polycyclic aromatic hydrocarbons are environmental contaminants which have been detected in airborne particulates, coal fly ash, diesel emission and carbon black photocopier toners. These compounds are metabolized Tn vitro to genotoxic agents through ring oxidation and/or nitroreduction. The details of these metabolic pathways are considered using 4-nitrobiphenyl, 1- and 2-nitronaphthalene, 5-nitro-acenaphthene, 7-nitrobenz[a]anthracene, 6-nitro-chrysene, 1-nitropyrene, 1,3-, 1,6- and 1,8-dinitro-pyrene, and 1-, 3- and 6-nitrobenzo[a] pyrene as examples ... 

Solana, R.P., Chinchilli, V.M., Wilson, J.D., Carter, W.H., Jr., and Carchman, R.A. (1987), Evaluation of the Interaction of Three Genotoxic Agents in Eliciting Sister-Chromatid Exchanges using Response Surface Methodology, Fundamental and Applied Tox., 9, 541-549. 

Grifoll M, Solanas AM, Bayona JM. 1992. Bioassay directed chemieal eharaeterization of genotoxic agents in the dissolved and particulate water phases of the Besos and Llobregat rivers (Barcelona, Spain). Arch Environ Contam Toxicol 23(1) 19-25. 

ETU was not a potent genotoxic agent in a variety of assays. At present, there is no threshold limit value (TLV) for ETU. ... 

Mirsalis JC, Butterworth BE. 1980. Detection of unscheduled DNA synthesis in hepatocytes isolated from rats treated with genotoxic agents an in vivo-in vitro assay for potential carcinogens and mutagens. Carcinogenesis 1 621-625. 

Unfortunately, there has been an uncritical acceptance of the notion that a positive result in a rodent bioassay automatically implies a carcinogenic risk for humans. While this may well be the case for genotoxic agents, for nongenotoxic substances there will be exceptions, especially if the proliferative response occurs only at high doses" (Cohen and Ellwein 1991, 903). 

Tyson, C.K. Mirsalis, J.C. (1985) Measurement of unscheduled DNA synthesis in rat kidney cells following in vivo treatment with genotoxic agents. Environ. Mutag., 7, 889-899... 

Suspect human carcinogen and known genotoxic agent Arecoline. One of the alkaloids present in betel nuts, the chewing of which leads to oral cancer (79MH0507, 82MI10503)... 

The test is based on the capability of genotoxic agents to induce the umuC-gene in the Salmonella strain in response to genotoxic lesions in the DNA. The induction of the umuC-gene is thus a measure for the genotoxic potential of the sample. 

The test is routinely undertaken with and without metabolic activation (S9), which allows detection of direct genotoxic agents, and those requiring metabolic activation to express their genotoxic potency (indirect genotoxicants). 

Biomarkers do not measure exposure directly, but are an indicator of absorbed dose. A biomarker of exposure is defined as a xenobiotic substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target molecules(s) or cell(s) that is measured within a compartment of an organism and can be related to exposure. Urine, blood, nail, saliva, hair, and faeces are common media collected for biomarker measurements. Maternal biomarkers of exposure can also be measured in amniotic fluid and breast milk. These matrices can also provide a measure of exposure for children, both prenatally and postnatally. Biomarkers in first teeth have also been used to assess early childhood exposure, whereas biomarkers in meconium and cord blood have been used to assess in utero exposures. Biomarkers of genetic damage (e.g. DNA adducts) have been extensively used to assess exposure to genotoxic agents (Neri et al., 2006). 

Pilliere F, Levy F, Renier A, et al. 1992. Induction of DNA-repair synthesis (UDS) in rat pleural mesothelial cells by urine of subjects exposed to genotoxic agents. Clin Toxicol 30(2) 223-238. 

Valid information on gene mutations, structure chromosome aberrations (clastogenicity) and numerical chromosome aberrations (aneugenicity) is required. No single test is capable of detecting all relevant genotoxic agents, therefore, a battery of tests is considered appropriate. 

Bermudez E, Mirsalis JC, Eales HC (1982) Detection of DNA damage in primary cultures of rat hepatocytes following In Vivo and In Vitro exposure to genotoxic agents. Environ Mutagen 4 667-679... 

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