Combinations of Genotoxic Tests for the Evaluation of Group 1 IARC Carcinogens
Many of the known human carcinogens are potent genotoxins that are efficiently detected as carcinogens in human populations but certain types of compounds such as immune suppressants, sex hormones etc. act via non-genotoxic mechanism. The absence of genotoxicity and the diversity of modes of action of non-genotoxic carcinogens make predicting their carcinogenic potential extremely challenging. There is evidence that combination of different short-term tests provide a better and efficient prediction of human genotoxic and non-genotoxic carcinogens. The purpose of this study is to summarize the in vivo and in vitro comet assay (CMT) results of group 1 carcinogens selected from International Agency for Research on Cancer (IARC) and to discuss the utility of the comet assay along with other genotoxic assays like Ames, in vivo micronucleus (MN), and in vivo chromosomal aberration (CA) test. Out of the 62 agents for which valid genotoxic data were available, 38/61 (62.3%) were Ames test positive, 42/60 (70%) were in vivo MN test positive and 36/45 (80%) were positive in vivo CA test. Higher sensitivity was seen in in vivo CMT (90%) and in vitro CMT (86.9%) assay. Combination of two tests has greater sensitivity than individual tests; in vivo MN + in vivo CA (88.6%), in vivo MN + in vivo CMT (92.5%), and in vivo MN + in vitro CMT (95.6%). Combinations of in vivo or in vitro CMT with other tests provided better sensitivity. In vivo CMT in combination with in vivo CA provided the highest sensitivity (96.7%).
Keywords - Carcinogens; comet assay; Micronucleus test; Ames test; Chromosomal aberration; Genotoxic test