INCREASED POLY(ADP-RIBOSE) POLYMERASE-ACTIVITY DURING REPAIR OF (PLUS-OR-MINUS)-ANTI-BENZO[A]PYRENE DIOLEPOXIDE-INDUCED DNA-DAMAGE IN HUMANPERIPHERAL-BLOOD LYMPHOCYTES IN-VITRO

Poly(ADP-ribose) polymerase, which catalyzes the formation of poly(ADP -ribose) polymers, is an enzyme involved in cell proliferation, differ entiation and transformation as well as in recovery from DNA damage. P oly(ADP-ribose) polymers are rapidly synthesized from the ADP-ribose m oieties from intracellular NAD(+), which, as a consequence, is deplete d. It has been shown that DNA strand breaks are required for enzyme ac tivation and it is suggested that one of the functions of poly(ADP-rib osylation) is to improve accessibility of damaged sites to other DNA r epair enzymes. The aim of this study was to investigate whether poly(A DP-ribosylation) is involved in repair of (+/-)-7 beta,8 alpha-dihydro xy-9 alpha,10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a] pyrene [(+/-)-a nti-BPDE]-induced DNA damage in human lymphocytes in vitro. Results sh ow that (+/-)-anti-BPDE is capable of inducing poly(ADP-ribosylation), NAD(+) depletion and inhibition of proliferation in phytohemagglutini n-stimulated human peripheral blood lymphocytes. Also, repair of (+/-) -anti-BPDE induced DNA damage was confirmed by both unscheduled DNA sy nthesis and (+/-)-anti-BPDE-deoxyguanosine adduct removal. Based on th ese findings, it is concluded that poly(ADP-ribosylation) is involved in (+/-)-anti-BPDE-induced DNA repair in these cells. In addition, the se results confirm the possible relation between poly(ADP-ribosylation ), NAD(+) depletion and inhibition of proliferation, after induction o f DNA damage.