The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer.
The effect of dietary folate on Apc and p53 mutations in the dimethylhydrazine rat model of colorectal cancer.
复制标题
膳食叶酸对二甲肼大鼠结直肠癌模型中 Apc 和 p53 突变的影响。
DOI：
10.1093/carcin/20.12.2345
复制
发表时间：
1999
期刊：
影响因子：
4.7
通讯作者：
Kim,YI
中科院分区：
文献类型：
--
作者：
Sohn,KJ;Puchyr,M;Salomon,RN;Graeme-Cook,F;Fung,L;Choi,SW;Mason,JB;Medline,A;Kim,YI
Dietary inadequacy of folate enhances and folate supplementation suppresses colorectal carcinogenesis in the dimethylhydrazine rat model. Folate is an essential factor for DNA methylation and thede novobiosynthesis of nucleotides, aberrations of which play important roles in mutagenesis. This study investigated whether the mutational hot spots of theApcandp53genes for human colorectal cancer are mutated in dimethylhydrazine-induced colorectal neoplasms and whether dietary folate can modulate mutations in these regions. Rats were fed diets containing 0, 2 (basal requirement), 8 or 40 mg folate/kg diet. Five weeks after diet initiation, dimethylhydrazine was injected weekly for 15 weeks. Mutations were determined by direct sequencing in 11 low and seven high grade dysplasias and 13 invasive adenocarcinomas. A total of sixApcmutations were found in four dysplastic and carcinomatous lesions: two in two low grade dysplasias, two in one high grade dysplasia and two in one adenocarcinoma. All mutations were single base substitutions, four of which were A:T→G:C transitions. Five of the six mutations were located upstream from the region corresponding to the humanAPCmutation cluster region. Dietary folate had no effect on the frequency and type ofApcmutations. No mutations were detected in exons 5–9 of thep53gene in neoplastic lesions. These data suggest that in the dimethylhydrazine rat model of colorectal cancer, theApcgene is mutated in early stages, albeit to a lesser degree than observed in human colorectal cancer, whereas the mutational hot spot of thep53gene for human colorectal cancer is not commonly mutated. Although the low frequency ofApcmutations and the small number of neoplasms studied in this study might have precluded our ability to observe modulatory effects of folate, dietary folate appears to have no significant effect onApcandp53mutations.
