THE EFFECT OF POLYAMINE DEPLETION ON THE CYTOTOXIC RESPONSE TO PUVA, GAMMA-RAYS AND UVC IN V79 CELLS IN-VITRO

Difluoromethylornithine (DFMO) depletes cells of polyamines, sensitizi ng cells against the action of antineoplastic drags and altering abili ty to repair radiation-induced DNA strand breaks. Others have hypothes ized that the mechanism by which polyamine depletion sensitizes cells is through inhibition of DNA strand break repair or through altering t he spectrum of initial DNA damage. We have compared the effect of poly amine depletion on cytotoxic effects in V79 cells for three agents tha t damage DNA: PUVA (8-methoxypsoralen and ultraviolet light, 365 nm), gamma-rays and UVC (ultraviolet light, 254 nm) in polyamine depleted V 79 cells. DFMO pretreatment sensitizes cells to PUVA and gamma-ray tox icity but not to UVC. Unlike WC photoinduction of DNA lesions, PUVA- a nd gamma-ray-induced DNA damage is modulated by chromatin structure. O ur results suggest that polyamine depletion sensitizes cells to the ac tion of PUVA and gamma-rays by mechanisms disparate from those for UVC , suggesting that the level or type of initial damage, rather than DNA repair, per se, may be the more important determinant of enhanced cyt otoxicity. (C) 1994 Academic Press, Inc.