Gingell R, Brunk G, Nagel D, Pour P
Cancer Res. 1979 Nov;39(11):4579-83.
The in vivo metabolism and disposition of three radiolabeled N-nitrosamines which are carcinogenic for the pancreas of the hamster but not the rat have been examined. N-[1-14C]Nitrosobis(2-oxopropyl)amine (BOP), N-[1-14C]nitrosobis(2-hydroxypropyl)amine (BHP), and their suggested proximate pancreatic carcinogenic metabolite N-[1-14C]nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) were metabolized and exhaled as 14CO2 to various extents somewhat proportional to their carcinogenic potency. More than 50% of the dose of BOP and HPOP was exhaled as 14CO2, whereas 26% of BHP was excreted this way, and 40% of BHP was excreted unchanged in the urine. Administered BOP was excreted to a small extent in the urine of both species as HPOP and BHP. No other nitrosamine metabolites were detected in urine. HPOP and BHP were detected in the pancreatic juice and bile of both species after administration of BOP and BHP. The results suggest that pancreatic ductular carcinogenesis in the hamster as a result of exposure to BOP is not due to secretion of carcinogenic metabolities in the pancreatic juice or reflux of bile containing nitrosamine metabolites into the ducts. Carcinogen metabolic activation appears to be by an oxidative pathway.
已对三种放射性标记的N-亚硝胺在体内的代谢和处置情况进行了研究，这三种N-亚硝胺对仓鼠胰腺具有致癌性，但对大鼠无致癌性。N-[1-¹⁴C]亚硝基双(2-氧代丙基)胺(BOP)、N-[1-¹⁴C]亚硝基双(2-羟丙基)胺(BHP)，以及它们推测的胰腺直接致癌代谢物N-[1-¹⁴C]亚硝基-(2-羟丙基)(2-氧代丙基)胺(HPOP)在体内进行了代谢，并以¹⁴CO₂的形式呼出，呼出程度在一定程度上与它们的致癌效力成正比。超过50%的BOP和HPOP剂量以¹⁴CO₂的形式呼出，而BHP以这种方式排出的比例为26%，40%的BHP以原形经尿液排出。给予的BOP在两种动物的尿液中均有少量以HPOP和BHP的形式排出。尿液中未检测到其他亚硝胺代谢物。给予BOP和BHP后，在两种动物的胰液和胆汁中均检测到了HPOP和BHP。结果表明，仓鼠因接触BOP而发生的胰腺导管癌变并非由于胰液中致癌代谢物的分泌或含亚硝胺代谢物的胆汁反流至导管所致。致癌物的代谢活化似乎是通过氧化途径进行的。
