Marnett L J, Hurd H K, Hollstein M C, Levin D E, Esterbauer H, Ames B N
Mutat Res. 1985 Jan-Feb;148(1-2):25-34. doi: 10.1016/0027-5107(85)90204-0.
Strains of Salmonella typhimurium that carry a nonsense mutation at the site of reversion detect a variety of naturally occurring and synthetic carbonyl compounds as direct-acting mutagens. TA104 is reverted efficiently by formaldehyde, alpha, beta-unsaturated aldehydes (enals), and dicarbonyl compounds, such as diacetyl and glutaraldehyde. This strain is much more sensitive to carbonyl mutagenesis than is TA100, a strain previously reported to detect aldehydes as mutagens, or any other characterized strains of Salmonella. Long-chain enals are very toxic to TA104, but addition of a reduced glutathione chase following an incubation period decreases this toxicity, thus enabling the detection of 4-hydroxy-pentenal, a homolog of the lipid peroxidation product, 4-hydroxy-nonenal, as a mutagen. This is the first report of the mutagenicity of a hydroxy-enal, a class of enals produced by lipid peroxidation. Testing conducted with strains that carry the nonsense mutation in different repair backgrounds indicates that the presence of pKM101 and the deletion of the uvrB gene facilitate the detection of enals and dicarbonyls, but not malondialdehyde, as mutagens. Since carbonyl compounds are widely distributed in foods, are generated during cellular metabolism, and are present in body fluids, they may make a significant contribution to the risk of human cancer.
在回复位点携带无义突变的鼠伤寒沙门氏菌菌株可将多种天然存在的和合成的羰基化合物检测为直接作用诱变剂。TA104可被甲醛、α,β-不饱和醛(烯醛)以及二羰基化合物(如双乙酰和戊二醛)有效回复突变。该菌株对羰基诱变作用的敏感性远高于TA100(一种先前报道可将醛检测为诱变剂的菌株)或任何其他已鉴定的沙门氏菌菌株。长链烯醛对TA104具有很强的毒性,但在孵育期后添加还原型谷胱甘肽可降低这种毒性,从而能够检测脂质过氧化产物4-羟基壬烯醛的同系物4-羟基戊烯醛作为诱变剂。这是关于羟基烯醛(一类由脂质过氧化产生的烯醛)诱变性的首次报道。在不同修复背景下携带无义突变的菌株所进行的测试表明,pKM101的存在以及uvrB基因的缺失有助于将烯醛和二羰基化合物(但不是丙二醛)检测为诱变剂。由于羰基化合物广泛分布于食物中,在细胞代谢过程中产生,且存在于体液中,它们可能对人类癌症风险有重大影响。