PMID: 7581488Jan 1, 1995Paper

Genetic polymorphisms and susceptibility to cancer development

Pharmacogenetics
T SugimuraM Nagao

Abstract

Humans show heterogeneous susceptibility to cancer development, suggesting the involvement of various genetic backgrounds in control of the production of endogenous carcinogens, the metabolism of carcinogens, the repair of DNA damage, cell proliferation and defence mechanisms including immune reactions. Gastric cancer is the major cancer in Japan. However, little is known about the genes linked with its development. In 1967, we found that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced gastric cancers in Wistar rats. Subsequently the Buffalo strain of rats was reported to be resistant to MNNG stomach carcinogenesis, while ACI rats were very sensitive. In a carcinogenesis study using F1 and F2 rats, we suggested that this trait of MNNG stomach carcinogenesis-resistance was regulated by a single autosomal dominant allele. The O6-methylguanine adduct levels in gastric mucosa induced by MNNG were the same in Buffalo and ACI rats, but cell proliferation induced by MNNG was much higher in ACI than Buffalo animals. Chromosome mapping of the gene responsible for susceptibility to MNNG-induced carcinogenesis is now in progress and its identification will hopefully give us clues to the involvement of genetic traits in susceptibility ...Continue Reading

Citations

Dec 12, 2001·British Journal of Clinical Pharmacology·A K Daly, C P Day
Nov 21, 2007·British Journal of Pharmacology·J-D MaréchalM J Sutcliffe
Jul 25, 2003·British Journal of Haematology·Leslie L Robison, Smita Bhatia

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