Radiation and Molecular Biology Unit, Department of Biochemistry, North-Eastern Hill University, Umshing, Shillong 793022, India.
Environ Toxicol Pharmacol. 2009 Jan;27(1):127-38. doi: 10.1016/j.etap.2008.09.003. Epub 2008 Sep 23.
Alteration of p53 protein level, and possible mutation of the p53 gene during carcinogenesis in mice exposed chronically (P) and transgenerationally to 2mg/ml aqueous extract of betel nut (AEBN) in drinking water, were studied. Exons 5 and 7 of the p53 gene were not mutated under both chronic and transgenerational exposure, but, p53 protein response was altered. In P mice, p53 protein was initially upregulated in comparison to age-matched controls, reaching 2.5 folds in the liver after 6 weeks of exposure. Subsequently, p53 protein declined to control level after 16 weeks, with concomitant preneoplastic nodulation of the liver. After 24 weeks, p53 protein was below control level, and preneoplastic nodules were well-developed. The level of p53 protein in transgenerationally exposed mice remained invariant in comparison to age-matched controls. Liver nodulation was significantly advanced, developing in F1 mice after 8 weeks, F2 mice after 6 weeks and F3 mice after 4 weeks of exposure. Anomalies not observed in P mice, developed in transgenerationally exposed mice, albeit, non-significantly. Thus, AEBN exposure enhanced transgeneration transmission of carcinogenic risk.
在慢性（P）和经代（transgenerationally）暴露于饮用水中 2mg/ml 槟榔水提取物（AEBN）的情况下，研究了暴露于慢性和经代暴露下的小鼠癌变过程中 p53 蛋白水平的改变，以及 p53 基因的可能突变。p53 基因的外显子 5 和 7 在慢性和经代暴露下均未发生突变，但 p53 蛋白反应发生了改变。在 P 小鼠中，p53 蛋白最初与年龄匹配的对照组相比上调，暴露 6 周后在肝脏中达到 2.5 倍。随后，p53 蛋白在 16 周后下降至对照水平，同时伴有肝前瘤性结节。24 周后，p53 蛋白低于对照水平，且前瘤性结节发育良好。与年龄匹配的对照组相比，经代暴露的小鼠中 p53 蛋白水平保持不变。肝结节明显提前，F1 小鼠在暴露 8 周后，F2 小鼠在暴露 6 周后，F3 小鼠在暴露 4 周后出现。在 P 小鼠中未观察到异常，但在经代暴露的小鼠中出现，尽管无统计学意义。因此，AEBN 暴露增强了致癌风险的跨代传递。
