Screening for colon carcinogens--a new strategy.

The major defect of in vivo assays for mutagenic carcinogens may be tissue specificity: a cancer bioassay of a single tissue would not be expected to detect all carcinogens, so the failure of a genetic assay in a single tissue to detect all carcinogens should not be surprising. In the search for an environmental carcinogen responsible for a specific cancer in a particular population, however, it may be that tissue specificity can be advantageous. Assays for genotoxicity directly in the target cells may have higher success rates with fewer false positives than assays in tissues of convenience. For example, to facilitate the search for one or more dietary carcinogens responsible for the high rate of colon cancer in North America, assays for genotoxicity in the target cells themselves, the colonic epithelium, may be useful. To this end we have investigated assays for three different endpoints: nuclear anomalies, sister chromatid exchanges, and gene mutations. Our experience may prove useful for others considering a similar strategy.