Vaughan P, Sedgwick B, Hall J, Gannon J, Lindahl T
Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Herts, UK.
Carcinogenesis. 1991 Feb;12(2):263-8. doi: 10.1093/carcin/12.2.263.
Many microorganisms exhibit an adaptive response to mutagenic alkylation damage. In Escherichia coli the response is regulated by the inducible Ada protein. A sensitive immunoassay employing two anti-Ada monoclonal antibodies has been developed here to monitor low levels of induction of the Ada protein. This protein was detected in non-induced E. coli which contained an average of two molecules of Ada per cell. The occurrence of the adaptive response in bacteria signals the existence of an ecological niche in which cells are exposed to direct-acting methylating compounds, but the structure and identity of these agents are unknown. Using the immunoassay to search for possible candidates, a number of methylating agents and precursors of such agents have been investigated. Carbamyl phosphate and methylamine yield N-methylurea, which reacts subsequently with nitrite to generate the strong inducer N-methyl-N-nitrosourea. The antibiotic streptozotocin also is a potent inducer of the adaptive response. Moreover, the abundant environmental mutagen methyl chloride acts as an inducer.
许多微生物对诱变烷基化损伤表现出适应性反应。在大肠杆菌中，这种反应由可诱导的Ada蛋白调节。本文开发了一种使用两种抗Ada单克隆抗体的灵敏免疫测定法，以监测Ada蛋白的低水平诱导。在未诱导的大肠杆菌中检测到了这种蛋白，每个细胞平均含有两个Ada分子。细菌中适应性反应的出现表明存在一个生态位，其中细胞暴露于直接作用的甲基化化合物，但这些物质的结构和身份尚不清楚。利用免疫测定法寻找可能的候选物，已对多种甲基化剂及其前体进行了研究。氨基甲酰磷酸和甲胺生成N-甲基脲，其随后与亚硝酸盐反应生成强诱导剂N-甲基-N-亚硝基脲。抗生素链脲佐菌素也是适应性反应的有效诱导剂。此外，环境中大量存在的诱变剂甲基氯也可作为诱导剂。
