Diwan B A, Rice J M, Ward J M
Biological Carcinogenesis and Development Program, Program Resources, Inc., Frederick, MD.
Prog Clin Biol Res. 1990;331:69-83.
Inbred strains of mice were found to differ significantly in their susceptibility to liver tumor promotion by PB. The susceptibility to promotion of hepatocarcinogenesis by this drug was a dominant trait in crosses between the sensitive DBA and resistant C57 mice. The reciprocal F1 hybrids responded similarly to tumor promotion by PB. PB promoted the development of hepatoblastomas in D2B6F1 males but not in B6D2F1 mice. Female mice of the D2B6F1 cross, similarly exposed to PB, failed to develop hepatoblastomas. These results suggested a sex-linked differential response to the development of hepatoblastomas in reciprocal F1 hybrids that are genetically identical except for the reverse origin of their X and Y chromosomes. Differences in the promoting effects of PB between C57 and DBA mice appeared to correlate with differences in the metabolism/detoxification of this drug. In conclusion, mouse strains that differ in susceptibility to two-stage liver carcinogenesis provide excellent opportunities to investigate the genetic and/or biochemical mechanisms responsible for these differences. Understanding these mechanisms may lead to the identification of factors that affect liver tumor development not only in mice but in other species as well.
人们发现，近交系小鼠对苯巴比妥（PB）促进肝脏肿瘤发生的易感性存在显著差异。在敏感的DBA小鼠和抗性的C57小鼠杂交中，这种药物促进肝癌发生的易感性是一个显性性状。正反交F1杂种对PB促进肿瘤发生的反应相似。PB促进了D2B6F1雄性小鼠肝母细胞瘤的发生，但在B6D2F1小鼠中则没有。同样暴露于PB的D2B6F1杂交雌性小鼠未发生肝母细胞瘤。这些结果表明，除了X和Y染色体起源相反外，遗传上相同的正反交F1杂种对肝母细胞瘤发生存在性别连锁的差异反应。C57和DBA小鼠之间PB促进作用的差异似乎与该药物代谢/解毒的差异相关。总之，对两阶段肝脏致癌易感性不同的小鼠品系为研究造成这些差异的遗传和/或生化机制提供了绝佳机会。了解这些机制可能不仅有助于识别影响小鼠肝脏肿瘤发生的因素，也有助于识别影响其他物种肝脏肿瘤发生的因素。
