Persistence of cisplatin-induced DNA interstrand crosslinking in peripheral blood mononuclear cells from elderly and young individuals

Abstract

DNA interstrand crosslinks (ISCL) produced by the incubation of human peripheral blood mononuclear cells (PBMs) with cisplatin (CDDP) were measured in two populations of volunteers, one aged less than 25 years and the other, greater than 72 years. The technique of fluorometric alkaline elution was used to measure DNA interstrand crosslinking with time after a 1-h exposure to drug. The samples from the young group showed a more consistent pattern of crosslink formation and removal, with extensive, or in some cases complete, repair at 48 h. Those from the elderly group showed considerable inter-individual variation and significantly higher mean levels of crosslinking at 24 and 48 h. No samples showed complete repair at 48 h in this population. These results indicate an impaired DNA repair capacity in the cells from the elderly group. This may be a factor in the poor tolerance of chemotherapy in the ageing population.