Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A.
The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclarcinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quandriradial chromosomal exchange fiqures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.
Steinheider
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G
Westendorf
J
J
Marquardt
H
H
D015250:Aclarubicin; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D002869:Chromosome Aberrations; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental; D051379:Mice; D009154:Mutation; D009279:Naphthacenes / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C024886:N,N-dimethyldaunorubicin; D015250:Aclarubicin; D003630:Daunorubicin