Bhave M R, Wilson M J, Poirier L A
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research Facility, MD 21701.
Carcinogenesis. 1988 Mar;9(3):343-8. doi: 10.1093/carcin/9.3.343.
The extent of methylation of the c-H-ras and c-K-ras oncogenes was compared in neoplastic and preneoplastic livers of rats fed one of several methyl-deficient, amino acid-defined diets for 18 months, with or without a preceding initiating dose of diethylnitrosamine (DEN). The restriction endonucleases MspI, HpaII, HhaI, PaeR71 and XhoI were used for studying the extent and pattern of DNA methylation. The results indicated that both c-H-ras and c-K-ras oncogenes were hypomethylated in all DNA samples derived from both neoplastic and preneoplastic livers of rats fed any of the methyl-deficient diets used, regardless of whether or not the rats had received an initiating dose of DEN. It thus appears that dietary methyl deficiency does indeed lead to hypomethylation of ras genes in the DNAs of the resulting tumors. However, the significance of this hypomethylation in the tumorigenic process is not clearly understood.
在喂食几种甲基缺乏、氨基酸限定饮食之一达18个月的大鼠的肿瘤性和肿瘤前肝脏中，比较了c-H-ras和c-K-ras癌基因的甲基化程度，这些大鼠在有或没有预先给予起始剂量二乙基亚硝胺（DEN）的情况下进行实验。限制性内切酶MspI、HpaII、HhaI、PaeR71和XhoI用于研究DNA甲基化的程度和模式。结果表明，在喂食任何一种所用甲基缺乏饮食的大鼠的肿瘤性和肿瘤前肝脏衍生的所有DNA样本中，c-H-ras和c-K-ras癌基因均发生低甲基化，无论大鼠是否接受过起始剂量的DEN。因此，饮食中的甲基缺乏似乎确实导致了所产生肿瘤DNA中ras基因的低甲基化。然而，这种低甲基化在肿瘤发生过程中的意义尚不清楚。
