Yusof M, Yildiz D, Ercal N
Department of Chemistry, University of Missouri-Rolla, 65401, USA.
Toxicol Lett. 1999 May 20;106(1):41-7. doi: 10.1016/s0378-4274(99)00014-4.
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.
5-氨基酮戊酸（ALA）是一种血红素前体，在急性间歇性卟啉症和铅中毒时会蓄积。研究表明，ALA可诱导自由基生成，并可能对蛋白质和DNA造成损伤。在本研究中，研究了ALA对DNA损伤的影响以及N-乙酰-L-半胱氨酸（NAC）、抗氧化酶过氧化氢酶（CAT）和超氧化物歧化酶（SOD）对其的预防作用。通过测量8-羟基-2'-脱氧鸟苷（oh8dG）形成的增加来定量DNA的氧化损伤。时间进程研究表明，ALA可导致中国仓鼠卵巢（CHO）细胞中oh8dG水平呈线性增加。然而，直接铅暴露并未导致oh8dG水平有任何可测量的增加。在存在NAC（1 mM）或抗氧化酶（10 u/ml SOD和10 u/ml CAT）的情况下，oh8dG水平恢复到相应的对照水平。这表明NAC和抗氧化酶具有保护作用。为了确定ALA对细胞增殖的影响，在不同浓度的ALA存在和不存在的情况下，孵育24小时结束时对细胞数量进行计数。结果表明，高达5 mM的ALA水平不会抑制细胞增殖。
