Zurlo J, Longnecker D S
J Natl Cancer Inst. 1983 Sep;71(3):523-8.
N-nitrosobis(2-oxopropyl)amine (BOP), a potent pancreatic carcinogen in hamsters that has failed to induce pancreatic tumors in rats, was studied for its effects on the DNA of both rat and hamster pancreas in order to relate DNA damage (as measured by alkaline elution) to carcinogenicity in vivo. At doses of 10, 20, and 40 mg BOP/kg, extensive DNA damage was detected in male Syrian golden hamster pancreas but Lewis rat pancreatic DNA was not affected. Only at doses of 100 mg BOP/kg or greater could pancreatic DNA damage in the rat be detected. DNA damage was also observed in both rat and hamster livers at 10, 20, and 40 mg BOP/kg. Alkaline elution analysis of DNA from isolated rat and hamster acinar cells treated in vitro with BOP revealed that only hamster acinar cell DNA was damaged. Rat acinar cell DNA was unaffected at all doses examined, up to 200 micrograms BOP/ml medium. Unscheduled DNA synthesis studies in cultured acinar cells confirmed the observations that BOP is genotoxic to hamster but not to rat acinar cells. The results strongly suggested that rat pancreas did not have the ability to metabolically activate BOP, which accounted for lack of both BOP-induced DNA damage and carcinogenicity in the rat.
N-亚硝基双(2-氧代丙基)胺(BOP)是一种对仓鼠有强烈致癌作用的胰腺致癌物，但未能在大鼠中诱发胰腺肿瘤。为了将DNA损伤(通过碱性洗脱测定)与体内致癌性联系起来，研究了其对大鼠和仓鼠胰腺DNA的影响。在BOP剂量为10、20和40mg/kg时，在雄性叙利亚金仓鼠胰腺中检测到广泛的DNA损伤，但Lewis大鼠胰腺DNA未受影响。仅在BOP剂量为100mg/kg或更高时，才能检测到大鼠胰腺DNA损伤。在BOP剂量为10、20和40mg/kg时，在大鼠和仓鼠肝脏中也观察到DNA损伤。对体外经BOP处理的分离大鼠和仓鼠腺泡细胞的DNA进行碱性洗脱分析，结果显示只有仓鼠腺泡细胞DNA受损。在高达200μg BOP/ml培养基的所有检测剂量下，大鼠腺泡细胞DNA均未受影响。对培养的腺泡细胞进行的非定标DNA合成研究证实了以下观察结果：BOP对仓鼠腺泡细胞具有遗传毒性，但对大鼠腺泡细胞无遗传毒性。结果强烈表明，大鼠胰腺没有代谢激活BOP的能力，这就是大鼠中缺乏BOP诱导的DNA损伤和致癌性的原因。
