PMID: 7030475Nov 1, 1981Paper

Mutagenicity, tumorigenicity, and electrophilic reactivity of the stereoisomeric platinum(II) complexes of 1,2-diaminocyclohexane

Cancer Research
W R LeopoldR H Earhart

Abstract

Without external activation, cis- and trans-dichlorodiammineplatinum(II) (DDP) and the cis, trans(-), and trans(+) forms of dichloro-1,2-diaminocyclohexaneplatinum(II) (DDCP) and sulfato-1,2-diaminocyclohexaneplatinum(II) (SHP) showed a 400-fold range of mutagenicity for Salmonella typhimurium TA100 and TA98; they were 2 to 10 times more mutagenic for strain TA100 than for strain TA98. With strain TA100, trans-DDP was less than 0.5% as mutagenic as the cis isomer, which produced 180 revertants/nmol. For the diaminocyclohexane complexes, mutagenic activity was strongly dependent on the stereoisomer of the diaminocyclohexane in the complex. Thus, with strain TA100, the trans(+) forms of DDCP and SHP produced 220 and 66 revertants/nmol, respectively, while the cis and trans(-) isomers induced only 10 and 5% as many revertants as the trans(+) forms. The SHP complexes were the most reactive toward DNA and produced a greater reduction in the transforming activity of Bacillus subtilis DNA after 3-hr reaction times than did the DDP or DDCP complexes. With 20-hr reaction times, all of the platinum complexes showed similar extents of reaction with DNA and caused approximately equal losses of transforming activity. The stereoisomeric form...Continue Reading

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