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Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay
Abstract:
The mutagenic activities of 79 carcinogens, noncarcinogens, and structurally related compounds toward Salmonella typhimurium strains TA1530, TA1535, and TA1538 and toward Saccharomyces cerevisiae D3 were investigated in the intraperitoneal host-mediated assay. Fewer than half of the carcinogens were mutagenic toward the Salmonella strains. The insensitivity of the system was most marked with the aromatic amine and polycyclic hydrocarbon procarcinogens. Under the test conditions, fewer than 10% of the carcinogens showed clear mutagenic activity toward S. cerevisiae D3. However, none of the noncarcinogens was significantly mutagenic toward either S. typhimurium or S. cerevisiae D3. Overall, the intraperitoneal host-mediated assay does not seem suitable for routine preliminary screening of large numbers of potential carcinogens. The median lethal doses to mice of 46 compounds were determined.
Insights
The intraperitoneal host-mediated assay showed limited mutagenic activity for many carcinogens against Salmonella and yeast. This assay is not ideal for routine screening of potential carcinogens.
Area of Science:
- Toxicology
- Microbiology
- Genetics
Background:
- Carcinogen identification is crucial for public health.
- Assessing mutagenic potential is a key step in carcinogen evaluation.
- Existing screening methods have limitations.
Purpose of the Study:
- To evaluate the mutagenic activity of 79 compounds using the intraperitoneal host-mediated assay.
- To compare the sensitivity of Salmonella typhimurium and Saccharomyces cerevisiae D3 to various carcinogens.
- To determine the suitability of this assay for preliminary carcinogen screening.
Main Methods:
- Intraperitoneal host-mediated assay in mice.
- Testing mutagenicity against Salmonella typhimurium strains TA1530, TA1535, and TA1538.
- Testing mutagenicity against Saccharomyces cerevisiae D3.
- Determination of median lethal doses for 46 compounds.
Main Results:
- Less than half of the tested carcinogens showed mutagenicity in Salmonella strains.
- Aromatic amines and polycyclic hydrocarbons were poorly detected as mutagens.
- Fewer than 10% of carcinogens were mutagenic to Saccharomyces cerevisiae D3.
- No noncarcinogens exhibited significant mutagenic activity.
Conclusions:
- The intraperitoneal host-mediated assay demonstrated low sensitivity for detecting mutagenicity of certain carcinogens.
- The assay is not recommended for routine preliminary screening of a large number of potential carcinogens.
- Further research may be needed to optimize in vivo mutagenicity testing methods.