Mutagenicity of eight anthracycline derivatives in five strains of Salmonella typhimurium.

The mutagenicity of eight anthracycline derivatives, doxorubicin (adriamycin, ADM), daunorubicin (DNR), rubidazone (zorubicin), detorubicin (DTR), 4'-epi-adriamycin (4' epi-ADM), AD 32, N-leucyl daunorubicin (N-leu DNR) and aclacinomycin A, has been tested on Salmonella typhimurium TA 100, Ta 98, TA 1535, TA 1537 and TA 1538. All but aclacinomycin A were mutagenic. Adriamycin and daunorubicin were mutagenic in all five strains, but only at very high doses (40-100 micrograms/plate) in TA 1535 and 1537. TA 98 was the most sensitive strain. In general S9 mix (liver homogenate) increased the mutagenicity of the low doses of both compounds. Zorubicin, 4'-epi-adriamycin and detorubicin were mutagenic for TA 98 and TA 100 and slightly mutagenic in TA 1538. They were also activated by S9 mix. N-leu DNR and AD 32 were slightly but significantly mutagenic for TA 98 and TA 1538 and were also activated by S9 mix. Aclacinomycin A lacked mutagenic activity in the five strains even at cytotoxic doses, both in the presence and absence of S9 mix. The results with AD 32 N-leu DNR and aclacinomycin A strengthen the hypothesis according to which amino moiety of the anthracycline glycosides is essential for mutagenesis.