Becker R A, Lu S S, Brésil H, Shank R C, Montesano R
Cancer Lett. 1985 Feb;26(1):17-24. doi: 10.1016/0304-3835(85)90168-5.
Kinetics of ethylation of target and non-target organ DNA in vivo by diethylnitrosamine (DEN) was compared in rats and Syrian golden hamsters, since published reports indicate a single dose of DEN induces both kidney and liver tumors in rats and almost exclusively respiratory tract tumors in hamsters. Following treatment with 200 mg DEN/kg, 7-ethylguanine (7-etG) was lost more rapidly from hamster than from rat liver DNA, while O6-ethylguanine (O6-etG) persisted longer in hamster than in rat liver DNA. DNA ethylation was not detected in rat lung (non-target organ), while both 7-etG and O6-etG were quantitated in hamster lung (target organ) following DEN treatment. DNA ethylation in rat kidney DNA was approximately 1/10 of that in liver by 200 mg DEN/kg, and the persistence of 7-etG and O6-etG differed only slightly in these tissues. Ethylation of hamster liver DNA by DEN at doses between 20 and 200 mg/kg, as measured by 7-etG and O6-etG was proportional to the dose of carcinogen up to 160 mg/kg; at larger doses DNA ethylation sharply increased. Differences in the persistence of O6-etG between DEN-treated rats and hamsters cannot solely account for species differences in the organotropism of DEN carcinogenesis.
比较了二乙基亚硝胺（DEN）在大鼠和叙利亚金仓鼠体内对靶器官和非靶器官DNA的乙基化动力学，因为已发表的报告表明，单剂量的DEN可诱发大鼠的肾脏和肝脏肿瘤，而在仓鼠中几乎仅诱发呼吸道肿瘤。用200 mg DEN/kg处理后，仓鼠肝脏DNA中7-乙基鸟嘌呤（7-etG）的消失速度比大鼠肝脏DNA更快，而O6-乙基鸟嘌呤（O6-etG）在仓鼠肝脏DNA中的持续时间比大鼠更长。在大鼠肺（非靶器官）中未检测到DNA乙基化，而在DEN处理后的仓鼠肺（靶器官）中同时检测到了7-etG和O6-etG。用200 mg DEN/kg处理时，大鼠肾脏DNA中的DNA乙基化约为肝脏中的1/10，并且7-etG和O6-etG在这些组织中的持续时间仅略有差异。通过7-etG和O6-etG测量，DEN以20至200 mg/kg的剂量对仓鼠肝脏DNA进行乙基化，在高达160 mg/kg的剂量下与致癌物剂量成正比；在更高剂量下，DNA乙基化急剧增加。DEN处理的大鼠和仓鼠之间O6-etG持续时间的差异不能完全解释DEN致癌作用在器官嗜性方面的种属差异。
