Rao K N, Shinozuka H, Kunz H W, Gill T J
Int J Cancer. 1984 Jul 15;34(1):113-20. doi: 10.1002/ijc.2910340120.
In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC-linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N-2-acetylaminofluorene (AAF), and the induction of gamma-glutamyltranspeptidase (GGT)-positive foci, bile-duct proliferation and oval-cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT-positive foci (from three to six per section) and extensive bile-duct and oval-cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT-positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bile-duct or oval-cell proliferation. Biochemical studies of the liver and testes showed that the grc homozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3H-thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.
在一项探究胚胎发生与致癌作用之间可能关系的研究中，我们检测了携带grc基因（一种与主要组织相容性复合体（MHC）相关的影响生长发育的基因复合体）的大鼠对已知与癌症诱导相关的细胞和生化变化发展的易感性。主要通过是否存在grc基因而有所不同的遗传相关品系大鼠被喂食含有0.02% N-2-乙酰氨基芴（AAF）的饲料，并对两组动物肝脏中γ-谷氨酰转肽酶（GGT）阳性灶、胆管增生和卵圆细胞增生情况进行评分。所有grc基因纯合的大鼠均表现出GGT阳性灶（每切片3至6个）以及广泛的胆管和卵圆细胞增生。相比之下，未携带grc基因的动物中只有27%的肝脏有GGT阳性灶，且数量较少（每切片1至3个）；没有胆管或卵圆细胞增生。对肝脏和睾丸的生化研究表明，grc基因纯合子具有与癌症发展相关的代谢异常：胆固醇生物合成增加；DNA合成增加，这可通过3H-胸腺嘧啶核苷掺入DNA的增强来表明；磷酸己糖（HMP）途径受到刺激，这可通过葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）水平升高来表明；以及循环脂蛋白水平降低。携带grc基因的大鼠对喂食AAF的形态学反应以及这些动物中存在的生化异常均与最终导致癌症的变化一致。因此，在大鼠中，生长发育控制的异常、对化学诱导癌症的易感性以及胆固醇生物合成的控制之间似乎存在关联。
