Lawson T, Nagel D
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68105-1065.
Carcinogenesis. 1988 Jun;9(6):1007-10. doi: 10.1093/carcin/9.6.1007.
The activation of N-nitrosobis(2-oxopropyl)amine (BOP) by pancreas acinar and duct tissue from Syrian hamsters and MRC-Wistar rats in vitro and in vivo was measured in terms of the production and repair of DNA damage. Hamsters were given BOP (1 X 10 mg/kg, s.c.). DNA single strand breaks (SSB) were measured over 2 weeks. Significantly more SSB were present in duct than in acinar tissue. Their persistence in the duct fragments was due to a slower rate of repair. In a related experiment, duct fragments were isolated from BOP-treated (1 X 10 mg/kg, s.c.) hamsters 24 h after exposure and cultured for 6 days, or were isolated 7 days after exposure. The extent of DNA damage was comparable in the two groups, indicating that the repair process(es) were still operative in cultured cells. Isolated duct fragments were exposed to either BOP or N-nitrosomethyl(2-oxopropyl)amine (MOP) in vitro. MOP produced significantly more DNA damage than BOP even at a 5-fold lower dose. This is consistent with the greater carcinogenicity of MOP in the pancreas. BOP produced significantly less DNA damage in the rat pancreas than in the hamster pancreas. The rate of repair was at least twice as fast in the rat pancreas as in the hamster pancreas. There did not appear to be any preference for acinar or duct tissue in rats as there was in hamsters. This procedure was validated in rats by the use of the rat pancreas carcinogen azaserine, which only produced DNA damage in rat acinar tissue.
通过测量叙利亚仓鼠和MRC-威斯塔大鼠胰腺腺泡和导管组织在体外和体内对N-亚硝基双（2-氧代丙基）胺（BOP）的活化情况，评估DNA损伤的产生和修复。给仓鼠皮下注射BOP（1×10毫克/千克）。在2周内测量DNA单链断裂（SSB）。导管组织中的SSB明显多于腺泡组织。它们在导管片段中的持续存在是由于修复速度较慢。在一项相关实验中，在暴露24小时后从接受BOP处理（1×10毫克/千克，皮下注射）的仓鼠中分离出导管片段并培养6天，或在暴露7天后分离。两组的DNA损伤程度相当，表明修复过程在培养细胞中仍在起作用。将分离的导管片段在体外暴露于BOP或N-亚硝基甲基（2-氧代丙基）胺（MOP）。即使剂量低5倍，MOP产生的DNA损伤也明显多于BOP。这与MOP在胰腺中更大的致癌性一致。BOP在大鼠胰腺中产生的DNA损伤明显少于仓鼠胰腺。大鼠胰腺的修复速度至少是仓鼠胰腺的两倍。与仓鼠不同，大鼠的腺泡或导管组织似乎没有任何偏好。通过使用大鼠胰腺致癌物重氮丝氨酸验证了该程序在大鼠中的有效性，重氮丝氨酸仅在大鼠腺泡组织中产生DNA损伤。
