Vorce R L, Goodman J I
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
J Toxicol Environ Health. 1991 Nov;34(3):385-95. doi: 10.1080/15287399109531575.
The male hybrid B6C3F1 mouse exhibits a 30% spontaneous hepatoma incidence, whereas the paternal C3H/He strain and the maternal C57BL/6 strain exhibit a 60% and a negligible incidence, respectively. In addition, both male and female B6C3F1 mice are extremely sensitive to chemical induction of hepatocarcinogenesis. The Ha-ras, Ki-ras, and myc oncogenes have been implicated in a variety of solid tumors. Specifically, Ha- and, less frequently, Ki-ras have been reported to be activated in B6C3F1 mouse liver tumors. The objective of this study was to examine a possible point of transcriptional control of Ha-ras, Ki-ras, and myc in all three mouse strains, our hypothesis being that these oncogenes may be primed for expression in the nascent liver of those strains exhibiting a high spontaneous hepatoma incidence. A positive correlation has been established between gene expression and the presence of DNase I hypersensitive sites. DNase I hypersensitive sites were observed in the Ha-ras and myc oncogenes in the three mouse strains. However, Ha-ras appears to possess an additional site in B6C3F1 and C3H/He as compared to C57BL/6. Similarly, the Ki-ras oncogene exhibited a DNase I hypersensitive site only in B6C3F1 and C3H/He mouse liver. These results indicate that the hepatoma-prone strains (B6C3F1 and C3H/He) may have a greater potential for Ha- and Ki-ras expression than does the non-hepatoma-prone strain (C57BL/6).
雄性杂交B6C3F1小鼠的自发肝癌发生率为30%，而父本C3H/He品系和母本C57BL/6品系的发生率分别为60%和可忽略不计。此外，雄性和雌性B6C3F1小鼠对化学诱导的肝癌发生极为敏感。Ha-ras、Ki-ras和myc癌基因与多种实体瘤有关。具体而言，据报道Ha-ras以及较少见的Ki-ras在B6C3F1小鼠肝肿瘤中被激活。本研究的目的是检查这三种小鼠品系中Ha-ras、Ki-ras和myc的转录控制可能位点，我们的假设是这些癌基因可能在自发肝癌发生率高的品系的新生肝脏中易于表达。基因表达与DNase I超敏位点的存在之间已建立正相关。在三种小鼠品系的Ha-ras和myc癌基因中观察到了DNase I超敏位点。然而，与C57BL/6相比，Ha-ras在B6C3F1和C3H/He中似乎有一个额外的位点。同样，Ki-ras癌基因仅在B6C3F1和C3H/He小鼠肝脏中表现出DNase I超敏位点。这些结果表明，肝癌易感品系（B6C3F1和C3H/He）可能比非肝癌易感品系（C57BL/6）具有更大的Ha-和Ki-ras表达潜力。
