Heddle J A, Kaul H K, Gingerich J D, Couch D B
Department of Biology, York University, Toronto, Ontario, Canada.
Mol Toxicol. 1987 Apr-Sep;1(2-3):235-45.
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.
单一组织的癌症生物检测预计无法检测到所有致癌物，因此单一组织的遗传检测未能检测到所有致癌物也就不足为奇了。然而，在寻找特定人群中导致特定癌症的环境致癌物时，组织特异性可能具有优势。与在方便取材的组织中进行检测相比，直接在靶细胞中进行遗传毒性检测可能具有更高的成功率和更少的假阳性。例如，为了便于寻找导致北美结肠癌高发率的一种或多种膳食致癌物，在靶细胞即结肠上皮细胞中进行遗传毒性检测可能会有所帮助。为此，我们研究了针对三个不同终点的检测方法：核异常、姐妹染色单体交换和基因突变。我们的经验可能对其他考虑采用类似策略的人有用。
