Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC).
Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC).
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携带影响发育 (GRC) 的 MHC 相关基因的大鼠对化学致癌物的易感性增强。
DOI：
10.1002/ijc.2910340120
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发表时间：
1984
影响因子：
6.4
通讯作者：
Gill3rd,TJ
中科院分区：
文献类型：
--
作者：
Rao,KN;Shinozuka,H;Kunz,HW;Gill3rd,TJ
在一种测试胚胎发生和癌症发生之间可能关系的方法中，我们检查了携带grc的大鼠的易感性，grc是一种影响生长和发育的MHC连锁基因复合物，对已知与癌症诱导相关的细胞和生化变化的发展。对主要因存在或不存在grc而不同的遗传相关菌株饲喂含有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）阳性灶的诱导、胆管增殖和卵圆细胞增殖进行评分。所有grc纯合子大鼠均显示GGT阳性病灶（每个切片3 - 6个）和广泛的胆管和卵圆细胞增殖。相比之下，只有27%的不携带grc的动物在肝脏中有GGT阳性病灶，并且这些病灶的数量较少（每个切片1 - 3个）;没有胆管或卵圆细胞增殖。肝脏和睾丸的生化研究表明，原始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，如3H-胸苷掺入DNA的增加所示;己糖单磷酸（HMP）途径刺激，如葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）水平增加所示;以及循环脂蛋白水平降低。携带grc的大鼠对喂食AAF的形态学反应和这些动物中存在的生化异常与最终导致癌症的变化一致。因此，在大鼠中，生长和发育控制中的畸变、对癌症化学诱导的敏感性和胆固醇生物合成控制之间似乎存在关系。
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 bileduct or oval‐cell proliferation. Biochemical studies of the liver and testes showed that the grchomozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of3H‐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.