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.
D015250:Aclarubicin; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D015251:Epirubicin; D009152:Mutagenicity Tests; D009153:Mutagens; D009279:Naphthacenes / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D009153:Mutagens; D009279:Naphthacenes; C038696:N-leucyldaunorubicin; C016163:valrubicin; D015251:Epirubicin; D015250:Aclarubicin; D004317:Doxorubicin; C017218:detorubicin; C002205:zorubicin; D003630:Daunorubicin