N-acetyl-L-cysteine protects against delta-aminolevulinic acid-induced 8-hydroxydeoxyguanosine formation.

ABSTRACT

5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in acute intermittent porphyria and lead poisoning. It has been shown that ALA induces free radical generation and may cause damage to proteins and DNA. In the present study, the effects of ALA on DNA damage and its prevention by N-acetyl-L-cysteine (NAC) and the antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) are investigated. Oxidative damage to DNA was quantitated by measuring the increase in 8-hydroxy-2'-deoxyguanosine (oh8dG) formation. The time-course study demonstrated that ALA causes a linear increase in oh8dG levels in Chinese hamster ovary (CHO) cells. However, direct lead exposure did not cause any measurable increase in oh8dG levels. In the presence of either NAC (1 mM) or antioxidant enzymes (10 u/ml SOD and 10 u/ml CAT), oh8dG levels returned to the corresponding control levels. This suggests a protective role for NAC and the antioxidant enzymes. To determine the effect of ALA on cell proliferation, cell numbers were counted at the end of 24 h of incubation in the presence and absence of ALA at different concentrations. Results showed that levels of ALA up to 5 mM do not inhibit cell proliferation.