Bailey E, Connors T A, Farmer P B, Gorf S M, Rickard J
Cancer Res. 1981 Jun;41(6):2514-7.
In addition to reacting with biologically important nucleophilic sites in DNA, alkylating agents also interact with amino acids in proteins. Measurements of the extent of formation of these alkyl amino acids may be used as a means of determining exposure to these compounds. The degree of S-methylation of cysteine in hemoglobin was studied following in vivo exposure of rats to methyl methanesulfonate, dimethylnitrosamine, and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. A linear dose-response curve was observed for methyl methanesulfonate over a 100-fold dose range. For dimethylnitrosamine, there was a threshold of doses where no methylation could be detected, and a curved dose-response curve was obtained. At high doses, the degree of methylation of hemoglobin cysteine was 7-fold lower than that with methyl methanesulfonate. In vivo, no alkylation could be observed with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; however, the existence of naturally occurring S-methylcysteine in the rat hemoglobin may have overshadowed small increases in alkylation arising from exposure to this compound. The natural occurrence of S-methylcysteine was studied in 13 species, and amounts ranging from 5.6 nmol/g globin (hamster) to 481 nmol/g globin (partridge) were observed. The reason for its occurrence is unknown but is under investigation.
除了与DNA中具有生物学重要性的亲核位点发生反应外，烷化剂还会与蛋白质中的氨基酸相互作用。对这些烷基化氨基酸形成程度的测量可作为确定接触这些化合物的一种手段。在大鼠体内暴露于甲磺酸甲酯、二甲基亚硝胺和5-(3,3-二甲基-1-三氮烯)咪唑-4-甲酰胺后，研究了血红蛋白中半胱氨酸的S-甲基化程度。在100倍剂量范围内，观察到甲磺酸甲酯呈线性剂量反应曲线。对于二甲基亚硝胺，存在一个检测不到甲基化的剂量阈值，并获得了一条曲线状的剂量反应曲线。在高剂量下，血红蛋白半胱氨酸的甲基化程度比甲磺酸甲酯低7倍。在体内，未观察到5-(3,3-二甲基-1-三氮烯)咪唑-4-甲酰胺的烷基化现象；然而，大鼠血红蛋白中天然存在的S-甲基半胱氨酸的存在可能掩盖了因接触该化合物而导致的烷基化的小幅增加。研究了13个物种中S-甲基半胱氨酸的天然存在情况，观察到其含量范围从5.6 nmol/g珠蛋白（仓鼠）到481 nmol/g珠蛋白（鹧鸪）。其出现的原因尚不清楚，但正在研究中。
