Ohgaki H, Kawachi T, Matsukura N, Morino K, Miyamoto M, Sugimura T
Cancer Res. 1983 Aug;43(8):3663-7.
Genetic control of the induction of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.
在易患胃癌的ACI大鼠、抗胃癌的布法罗大鼠及其F1和F2代后代中,研究了N-甲基-N'-硝基-N-亚硝基胍(MNNG)诱导胃癌的遗传控制。所有品系的雌雄大鼠,初始年龄为7至9周,在其饮用水中给予浓度为83微克/毫升的MNNG,持续32周,并在实验第72周处死。ACI大鼠中胃腺癌的发病率在雄性中为80%,在雌性中为47%;在布法罗大鼠中,发病率在雄性中为18%,在雌性中为0%。F1杂种对MNNG的抗性与布法罗大鼠相同;胃腺癌的发病率在雄性中为17%,在雌性中为8%。这些结果表明,对MNNG诱导胃腺癌的抗性是一个显性特征。F2代中胃腺癌的发病率在雄性中为36%,在雌性中为14%,这接近单个抗性基因分离预期的3:1比例。在ACI和布法罗品系及其杂种中,雄性比雌性更易受MNNG诱导胃癌。在两个品系及其杂种中,肠道肿瘤主要在十二指肠和空肠中观察到,发病率如下:ACI:雄性67%,雌性42%;布法罗:雄性12%,雌性18%;F1:雄性18%,雌性15%;F2:雄性15%,雌性19%。因此,MNNG诱导胃癌和肠癌似乎存在共同的遗传基础。