Labeled 1,N6-ethenoadenosine and 3,N4-ethenocytidine in hepatic RNA of mice given[ethyl-1,2(-3)H or ethyl-1(-14)C]ethyl carbamate (urethan).
Labeled 1,N6-ethenoadenosine and 3,N4-ethenocytidine in hepatic RNA of mice given[ethyl-1,2(-3)H or ethyl-1(-14)C]ethyl carbamate (urethan).
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给予[乙基-1,2(-3)H 或乙基-1(-14)C]乙基氨基甲酸酯（尿烷）的小鼠肝 RNA 中标记有 1,N6-乙烯基腺苷和 3,N4-乙烯基胞苷。
DOI：
10.1093/carcin/3.5.539
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发表时间：
1982
期刊：
影响因子：
4.7
通讯作者：
Timmins,LG
中科院分区：
文献类型：
--
作者：
Ribovich,ML;Miller,JA;Miller,EC;Timmins,LG
将单剂量的[乙基-1,2-3H]或[乙基1-1-14C]-乙基氨基甲酸酯注射到12日龄雄性[C57BL/6 × C3H/He]F1小鼠中或将[乙基-1,2-3H]乙基氨基甲酸酯注射到成年雄性A/Jax小鼠中，导致标记的1,N6-乙烯基腺苷和3,N4-乙烯基胞苷的形成肝RNA中的加合物。这些加合物通过在高压液相色谱上共迁移来表征。具有合成标准品的 RNA 酶水解产物中的 3 H 或 14 C。乙烯腺苷和乙烯胞苷均通过转化为与乙酰化合成标准品共迁移的乙酰化产物来进一步表征。乙烯腺苷也被无水三氟乙酸转化为与合成的 1,N6-乙烯腺嘌呤共迁移的产物。单次注射 0.5-0.6 mg 氨基甲酸乙酯/g 体重 12 小时后，肝脏 RNA 中的加合物水平分别为 6-10 pmol/mg RNA 乙烯腺苷和 2-3 pmol/mg RNA 乙烯胞苷。给予[1-14C]乙醇（一种氨基甲酸乙酯的酶解产物）的小鼠的肝脏RNA中未检测到标记的乙烯腺苷或乙烯胞苷。这些数据表明氨基甲酸乙酯可以通过脱氢为氨基甲酸乙烯酯并随后如先前提出的后者化合物的环氧化而被代谢活化。乙烯基氨基甲酸酯环氧化物可以以类似于环氧氯乙烷（氯乙烯的亲电代谢物）所证明的方式形成乙烯衍生物。氨基甲酸乙烯酯已被证明具有与氨基甲酸乙酯相同的肿瘤诱导谱，但比后者的致癌物质活性高得多。
Injection of a single dose of [ethyl-1,2-3H] or [ethy1-1-14C]-ethyl carbamate into 12-day old male [C57BL/6 × C3H/He]F1mice or of [ethyl-1,2-3H]ethyl carbamate into adult male A/Jax mice resulted in the formation of labeled 1,N6-ethenoadenosine and 3,N4-ethenocytidine adducts in the hepatic RNA. These adducts were characterized by comigration on h.p.l.c. of3H or14C in enzymatic hydrolysates of the RNA with synthetic standards. Both the ethenoadenosine and ethenocytidine were further characterized by their conversion to acetylated products that comigrated with acetylated synthetic standards. The ethenoadenosine was also converted by anhydrous trifluoroacetic acid to a product that comigrated with synthetic 1,N6-ethenoadenine. The levels of adducts in the hepatic RNA 12 h after a single injection of 0.5–0.6 mg of ethyl carbamate/g body weight were 6–10 and 2–3 pmol/mg RNA of ethenoadenosine and ethenocytidine, respectively. No labeled ethenoadenosine or ethenocytidine could be detected in the hepatic RNA of mice given [1-14C]ethanol, an enzymatic hydrolysis product of ethyl carbamate. These data indicate that ethyl carbamate may be metabolically activated by dehydrogenation to vinyl carbamate and subsequent epoxidation of the latter compound as previously proposed. Vinyl carbamate epoxide may form etheno derivatives in a manner analogous to that demonstrated for chloroethylene oxide, an electrophilic metabolite of vinyl chloride. Vinyl carbamate has been shown to have the same spectrum of tumor induction as ethyl carbamate but to be much more active than the latter carcinogen.