Detection of mammalian carcinogens with an immunological DNA synthesis-inhibition test.

Abstract

There is a close relationship between genotoxicity, mutagenicity and carcinogenicity. But the controversy of which short-term test system best recognizes human carcinogens is still going on. Currently, the Salmonella gene mutation assay ('Ames test') is the most widely used test for the screening of mutagens. However, many in vitro tests hold unsatisfactory validity data, presumably because of the inability of present short-term tests to detect non-genotoxic carcinogens, which are increasingly being brought into focus in the discussions of genesis of cancer. One principle often neglected in this context is the property of genotoxic agents to inhibit replicative DNA synthesis in (proliferating) eukaryotic cells. We believe that this early response to DNA damage is important in the multistage process of carcinogenesis. Accordingly, we proposed that a DNA synthesis-inhibition test should be included in the test batteries for carcinogen screening. In this paper we report the development of an appropriate DNA synthesis-inhibition test based on immunological techniques.