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Nuclear aberrations as a short-term test for genotoxicity to the colon: evaluation of nineteen agents in mice
Abstract:
The genotoxicity of 16 agents including several hydrazines, nitrosamines, aromatic amines, polycyclic hydrocarbons, and other related compounds and three known inhibitors of carcinogenesis was assessed in the murine colonic nuclear aberration assay. Of the seven agents considered positive for colonic DNA damage, five were large bowel carcinogens. All structural analogues of the intestinal carcinogens that are tumorigenic for other organs, with the exception of benzo[a]pyrene, were negative in the colonic nuclear aberration assay as were all noncarcinogens tested. The metabolic inhibitor disulfiram completely inhibited 1,2-dimethylhydrazine-induced colonic nuclear damage, while inhibition was less marked for the antioxidants butylated hydroxyanisole and caffeic acid. The versatility of the assay as an indicator of colonic genotoxicity resulting from carcinogen exposure is discussed.
Insights
The murine colonic nuclear aberration assay identified genotoxicity in five large bowel carcinogens among 16 tested agents. This assay effectively indicates genotoxicity from carcinogen exposure, with some inhibitors showing protective effects.
Area of Science:
- Toxicology
- Carcinogenesis
- Molecular Biology
Background:
- Genotoxicity testing is crucial for identifying potential carcinogens.
- The murine colonic nuclear aberration assay is a tool for assessing DNA damage in the colon.
- Understanding the genotoxic effects of various chemical compounds is vital for public health.
Purpose of the Study:
- To evaluate the genotoxicity of 16 diverse chemical agents using the murine colonic nuclear aberration assay.
- To determine the assay's efficacy in identifying large bowel carcinogens.
- To investigate the inhibitory effects of specific compounds on carcinogen-induced DNA damage.
Main Methods:
- The study utilized the murine colonic nuclear aberration assay.
- Sixteen agents, including hydrazines, nitrosamines, aromatic amines, and polycyclic hydrocarbons, were tested.
- Inhibitors of carcinogenesis, such as disulfiram and antioxidants, were used to assess their modulatory effects.
Main Results:
- Seven agents induced colonic DNA damage, with five identified as large bowel carcinogens.
- Structural analogues of intestinal carcinogens, except benzo[a]pyrene, were negative in the assay.
- Disulfiram significantly inhibited 1,2-dimethylhydrazine-induced damage, while antioxidants showed less inhibition.
Conclusions:
- The murine colonic nuclear aberration assay is a versatile tool for detecting colonic genotoxicity.
- The assay demonstrated specificity in identifying large bowel carcinogens.
- Metabolic inhibitors can modulate carcinogen-induced genotoxicity in the colon.