Molecular and Cellular Aspects of Chemical Carcinogenesis

Different DNA-adducts produced by one given genotoxic agent can lead to different mutational preferences, as exemplified in this mini-review, by the cis-diamminedichloroplatinum(II)-induced d(GpG)-N7(1)-N7(2) adduct, giving rise predominantly to G→T transversions targeted to the 5′-modified G, the d(ApG)-N7(l)-N7(2) adduct to A→T transversions, while for the d(GpTpA)-N7(l)-N7(3) adduct no crosslink-specific mutations were observed. Expression of mutated Hras put under the control of cell-compartment specific promoters in different layers of the mouse skin showed that the consequent expression of the malignant phenotype depended on the degree of differentiation of the cell, progression to ca…