Genotoxicity of the antitumor antibiotic CC-1065.
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| Abstract |
CC-1065, a very potent antitumor antibiotic, is active against several animal tumors, and against human tumors in the cloning assay at doses 50-1000 times lower than other agents such as adriamycin. It binds and alkylates DNA, and inhibits DNA synthesis, suggesting a potential for genotoxicity. Therefore, the genotoxic effects of CC-1065 were tested in several assay systems. CC-1065 was weakly mutagenic in the Ames Salmonella mutation assay (strain TA100) without S9 activation, but lacked mutagenic activity in TA98 with or without activation. CC-1065 was a very potent mutagen in the Salmonella forward mutation assay (induction of 8-azaguanine resistance), increasing the mutation frequency 19-fold over background at 0.1 ng/ml without activation. In mammalian (V79) cells it was a very potent mutagen without activation, increasing the mutation frequency 20-fold over background a 0.5 ng/ml. CC-1065 induced chromosome aberrations in V79 cells at very low (less than 0.1 ng/ml) doses, making this assay the most sensitive. CC-1065 increased the induction of micronuclei in rats 10- to 20-fold over the background at 200 and 400 micrograms/kg, but not at 100 micrograms/kg. CC-1065 failed to cause DNA breaks or DNA--protein cross-links as measured by the DNA damage/alkaline elution assay.
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| Authors | P R Harbach, R J Trzos, J H Mazurek, D M Zimmer, G L Petzold, B K Bhuyan |
| Journal | Mutagenesis (Mutagenesis) Vol. 1 Issue 6 Pg. 407-10 (Nov 1986) ISSN: 0267-8357 [Print] England |
| PMID | 3331678 (Publication Type: Journal Article) |
| Chemical References |
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