ABSTRACT The damage formed in DNA of CHO cells by UVA irradiation in the presence of linear and angular furocoumarins was studied using alkaline elution. All compounds were able to induce single-strand breaks into DNA: the more effective derivatives appeared to be 3-carbethoxypsoralen and 3-carbethoxyangelicin. As known, linear furocoumarins, (e.g., psoralen) appeared to be good DNA cross-linkers, while some angular ones (e.g., angelicin and 4,4’-dimethylangelicin) did not induced inter-stand cross-links; however, 4,6,4’-trimethylangelicin, described as a pure monofunctional compound, induced significant amounts of inter-stand cross-links. High numbers of DNA-protein cross-links were observed with psoralen and 8-methoxypsoralen., while 4,4’-dimethylangelicin seemed to be less effective; all other compounds including 4,6,4’-trimethylangelicin, did not form any DNA-protein cross-link. Experiments carried out with the two steps irradiation and 8-methoxypsoralen gave results consistent with the formation of DNA-protein cross-links by a two steps mechanisms in which the furocoumarin moiety forms a bridge between the two macromolecules, thus resembling the inter-stand cross-link formation. Comparing these results with the capacity of the examined compounds of inducing skin-erythemas, a good correlation between this property and DNA-protein cross-linking ability was observed.
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