EXPERIMENTAL DATABASES ON INHIBITION OF THE BACTERIAL MUTAGENICITY OF4-NITROQUINOLINE 1-OXIDE AND CIGARETTE-SMOKE

Two antimutagenicity databases were prepared by applying a co-treatmen t procedure to the Salmonella reversion assay. Ninety compounds belong ing to various chemical classes were quantitatively tested for antimut agenicity towards the direct-acting mutagen 4-nitroquinoline 1-oxide ( 4NQO) in strain TA100 of S. typhimurium and 63 of them were additional ly tested for antimutagenicity towards unfractionated mainstream cigar ette smoke (CS) in strain TA98, in the presence of S9 mix. Twelve comp ounds (13.3%) inhibited 4NQO mutagenicity by at least 50%, with a MID5 0 (dose inhibiting 50% of mutagenicity) varying over a 1226-fold range . Twenty-six compounds (41.3%) inhibited CS mutagenicity, with a MID50 varying over a 520-fold range. Three compounds only, i.e., bilirubin, curcumin and myricetin, were capable of inhibiting the mutagenicities of both 4NQO and CS. However, myricetin and the other flavonoid rutin were at the same time mutagenic by inducing frameshift mutations foll owing metabolic activation. There was a rather rigorous selectivity of antimutagenicity data depending on the chemical class of inhibitors a nd it was possible to discriminate protective effects within several p airs or series of structurally related compounds. For instance, all ei ght thiols and aminothiols inhibited 4NQO mutagenicity, which contrast ed with the inactivity of the remaining 17 sulfur compounds tested, al l of them lacking a free sulfhydryl group. The mutagenicity of CS was consistently inhibited by the majority of phenols (eight out of 10 tes ted) and by all two isothiocyanates, two dithiocarbamates, three indol e derivatives, three tetrapyrrole compounds and three flavonoids teste d. Although the results obtained cannot be extrapolated to other mutag ens or test systems, they may provide a useful source of information f or research in the area of antimutagenesis and for the development of chemopreventive agents.