COMPARATIVE GENOTOXICITY OF ADRIAMYCIN AND MENOGAROL, 2 ANTHRACYCLINE ANTI-TUMOR AGENTS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (11) , 5293-5297
Abstract
Adriamycin and menogarol are anthracyclines with antineoplastic activity. Unlike adriamycin, menogarol does not bind strongly to DNA, and it minimally inhibits DNA and RNA synthesis at lethal doses. Adriamycin is a clinically active drug, and menogarol is undergoing preclinical toxicology testing. The genotoxicity of the 2 drugs was compared. Although adriamycin and menogarol differ significantly in their bacterial mutagenicity (Ames assay [Salmonella typhimurium]), they have similar genotoxic activity in several mammalian systems [mouse liver S9]. Adriamycin is strongly mutagenic in the Ames assay with TA98 and TA100. Menogarol is nonmutagenic to TA98 and TA100. For the mammalian cell culture systems, V79 (Chinese hamster) cells are exposed for 2 h to drug, following which cell surivival, induction of sister chromatid exchange, chromosome damage, and production of mutants resistant to 6-thioguanine are measured. The percentage of survival obtained with the 2 drugs ranges between 25 and 50% at 0.15 .mu.g/ml and 5-15% at 0.3 .mu.g/ml. At 0.15 .mu.g/ml, adriamycin and menogarol increase the percentage of cells with chromosome damage from a background level of 8.8-30 and 22.5%, respectively. The same drug concentration causes a small but significant increase in sister chromatid exchange rate. Both drugs are equally active (increase mutation frequency about 3- to 6-fold above background) in producing 6-thioguanine-resistant mutants. The induction of micronuclei in polychromatic erythrocytes of rats is the most sensitive assay system. Both drugs cause a 10- to 15-fold increase in micronuclei at nontoxic doses.