PMID: 9433479Jan 20, 1998Paper

Effect of dietary fat on codon 12 and 13 Ha-ras gene mutations in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced rat mammary gland tumors

Molecular Carcinogenesis
S J Roberts-Thomson, E G Snyderwine

Abstract

Activating mutations in and expression of the Ha-ras gene were examined in benign and malignant female Sprague-Dawley rat mammary gland tumors induced by the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by a diet high in polyunsaturated fat. Ha-ras mutations were detected in codons 12 and 13 by selective polymerase chain reaction amplification of mutated sequences and nucleotide sequencing. The percentage of Ha-ras mutations in carcinomas from PhIP-treated rats was significantly higher in rats on a low-fat diet than in rats on a high-fat diet (82% (nine of 11) vs 26% (seven of 27), respectively, P < 0.01). In addition, whereas 56% of the carcinomas with Ha-ras mutations from rats on a low-fat diet carried double Ha-ras mutations, none of the carcinomas from rats on a high-fat diet had double mutations. Ha-ras mutations were also detected in benign tumors (largely adenomas) induced by PhIP in rats on different diets; two of eight and three of four benign tumors examined from rats on low-fat and high-fat diets, respectively, had Ha-ras mutations, suggesting that activating Ha-ras mutations alone are not sufficient for PhIP-induced tumors to become malignant. No differences were observed i...Continue Reading

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Citations

Sep 28, 2002·Mutation Research·Eriko OkochiToshikazu Ushijima
Jan 8, 1999·Breast Cancer Research and Treatment·S J Roberts-Thomson, E G Snyderwine
Aug 21, 2007·International Journal of Radiation Oncology, Biology, Physics·Tatsuhiko ImaokaYoshiya Shimada
Feb 3, 2005·International Journal of Cancer. Journal International Du Cancer·Tatsuhiko ImaokaYoshiya Shimada
Oct 20, 2005·Cancer Science·Hitoshi NakagamaMasako Ochiai
Oct 10, 2013·International Journal of Cancer. Journal International Du Cancer·Tatsuhiko ImaokaYoshiya Shimada
Feb 24, 2001·The Journal of Nutrition·P Greenwald

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