L-arabinose resistance test with Salmonella typhimurium as a primary tool for carcinogen screening

The L-arabinose resistance test with Salmonella typhimurium (Ara test) is a forward mutation assay which selects a single phenotypic change (from L-arabinose sensitivity to L-arabinose resistance) in a unique tester strain (an araD mutant). The present study examined the ability of the Ara test to identify as mutagens different classes of chemical carcinogens, including six with detection problems in most bacterial assays. A noncarcinogen related in chemical structure to the selected carcinogen was included whenever possible. A total of 25 organic compounds was assayed by means of a standard mutagenesis procedure: the plate-incorporation test in the presence (if required) of 10% S9 from rat liver induced with Aroclor 1254. Chemicals giving negative or inconclusive results were then retested using other common in vitro mutagenesis conditions. The Ara test detected as mutagens all but one (Urethane) of the 15 established carcinogens and six out of the nine chemicals with questionable or nonassayed carcinogenicity. The compound mutagenic at the lowest dose was ethionine (0.57 nmol), one of the carcinogens undetected by the popular histidine reverse mutation assay (Ames test) or by the SOS chromotest. Actually, only benzo(a)pyrene was found mutagenic at a dose (0.77 nmol) close to that of ethionine. The data reported in this paper suggest that the Ara forward mutation test is less prone than the His reverse mutation test or the SOS chromotest to misclassify as negative carcinogenic compounds. Consequently, it should be considered as an alternative to other bacterial assays in general, massive, and primary screening for genotoxic carcinogens.