Mutagenesis by 9,10-anthraquinone derivatives and related compounds in Salmonella typhimurium

Ninety 9,10-anthraquinone (AQ) derivatives and related anthracene derivatives were screened for mutagenicity with five Salmonella typhimurium tester strains with and without mammalian microsomal activation. About 35% of the compounds tested are considered to be mutagenic. Three patterns of mutagenesis were apparent. (1)Direct frameshift mutagenesis by certain AQ compounds bearing free hydroxyl groups. The most potent were anthragallol (1,2,3-trihydroxy-AQ), purpurin (1,2,4-trihydroxy-AQ) and anthraufin (1,5-dihydroxy-AQ). Some hydroxy-AQ compounds exhibited activation by mammalian microsomal preparations, particularly at lower concentrations, and the majority of mutagenic hydroxy-AQs appeared to revert strain TA1537 (his 3076) specifically.(2)Frameshift mutagenesis by certain AQ compounds with primary amino and, in a few cases, with secondary amino groups. Mammalian microsomes invariably potentiated frameshift mutagenesis, and activity with strain TA100 (sensitive to base pair substitution) is seen in a few cases, e.g. 1,2-diamino-AQ. (3)AQ compounds with one or more nitro groups. These derivatives exhibit the least specificity with regard to tester strain reverted and to microsomal activation. All seven nitro-AQ's tested were mutagenic. In those compounds with mixed "mutagenic" functional groups, the type of mutagenesis observed is usually N02 greater than 0H greater than NH2. AQs bearing halogens, sulfonate or alkyl groups were non-mutagenic, as were AQs substituted solely with secondary amines.