Cytogenetic toxicity of antitumor platinum compounds in Fanconi's anemia

摘要

Peripheral blood lymphocytes of patients with Fanconi's anemia (FA) were tested for their susceptibility to chromosome breakage bycis-platinum(II)-diamminedichloride cis-Pt(II),cis-platinum(IV)diamminetetrachloride cis-Pt(IV), andtrans-platinum(IV)diamminetetrachloride trans-Pt(IV). Low doses (0.1 μg/ml) of the DNA-DNA cross-linking agentscis-Pt(II) andcis-Pt(IV) dramatically increased the chromosome breakage level in FA cultures without affecting the controls. The predominantly DNA-protein cross-linking compoundtrans-Pt(IV), however, was much less effective in producing chromosomal damage in FA. The differential response of FA cells tocis-Pt(IV) andtrans-Pt(IV) suggests that the high susceptibility of FA to bifunctional cross-linking agents is due to an impairment of the cells to tolerate DNA-DNA cross-links, rather than DNA-protein cross-links