PROOXIDANT EFFECTS OF DELTA-AMINOLEVULINIC-ACID (DELTA-ALA) ON CHINESE-HAMSTER OVARY (CHO) CELLS

delta-Aminolevulinic Acid (delta-ALA) is a heme precursor accumulated in lead poisoning and acute intermittent porphyria. Although no single mechanism for lead toxicity has yet been defined, recent studies sugg est at least some of the lead-induced damage may originate from delta- ALA-induced oxidative stress. The present study was designed to test t he hypothesis that delta-ALA accumulation in Chinese hamster ovary (CH O) cells contributes to the cumulative oxidative challenge of lead poi soning as indicated by the oxidative stress parameters glutathione (GS H), glutathione disulfide (GSSG), malondialdehyde equivalents (MDA), a nd catalase (CAT). It will also examine the possibility that this oxid ative challenge can be reversed by treatment with an antioxidant such as N-acetylcysteine (NAG). First in vitro administration of delta-ALA to CHO cells was found to have a concentration-dependent inhibitory ef fect on colony formation and cell survival. NAC administration was sho wn to alleviate this inhibition in CHO survival. The oxidative status of CHO cell cultures exposed to increasing concentrations of delta-ALA was then examined. Decreases in GSH levels (P<0.05) were observed in the delta-ALA-treated cultures as compared to the controls, while GSSG and MDA levels were significantly increased in delta-ALA-treated cell s (P<0.05), CAT activity was not significantly affected. NAC administr ation concurrent with delta-ALA exposure resulted in GSH and GSSG leve ls similar to the control levels, while no significant improvement in MDA was observed. These results indicate a stale of oxidative stress a nd suggest that the delta-ALA-induced inhibitory effect on CHO colony formation may be due to its pro-oxidant effect. To assess whether this oxidative challenge would induce antioxidant increases during extende d exposure to delta-ALA, CHO cells were exposed to 5 mM delta-ALA for increasing time periods. The GSH and GSSG levels were measured and a r ebound effect was observed after 12 h of delta-ALA exposure. (C) 1997 Elsevier Science Ireland Ltd.