Mutagenicity, cytotoxicity and DNA crosslinking in V79 Chinese hamster cells treated with cis- and trans-Pt(II) diamminedichloride.
The mutagenicity and cytotoxicity of cis- and trans-Pt(II) diamminedichloride (PDD) were examined in V79 Chinese hamster lung cells and compared with effects on DNA measured by alkaline elution. DNA--protein crosslinks and DNA interstrand crosslinks were detected following doses of cis-PDD which reduced cell survival 80--90% and which produced a mutant frequency of 3 X 10(-4) at the HGPRT locus. Equitoxic doses of trans-PDD were much less mutagenic than cis-PDD. At equitoxic doses, trans-PDD produced more DNA-protein crosslinking than did cis-PDD, but interstrand crosslinking for the two isomers was comparable. Hence, the interstrand crosslink could be the cytotoxic lesion produced by these Pt compounds whereas neither of these DNA lesions are necessarily mutagenic. The mutagenesis produced by cis-PDD could be due to crosslinks of a different type than those produced by trans-PDD or it may be due to monofunctional damage.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D055598:Chemical Phenomena; D002621:Chemistry; D002945:Cisplatin / Q000494:pharmacology*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008168:Lung; D009154:Mutation / Q000187:drug effects*; D010447:Peptide Hydrolases; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004247:DNA; D010447:Peptide Hydrolases; D002945:Cisplatin