Dietary N-3 fatty acids do not affect induction of Ha-ras mutations in mammary glands of NMU-treated rats.
The purpose of this study was to determine whether dietary n-3 polyunsaturates (PUFA) can affect the frequency of N-nitrosomethylurea (NMU)-induced Ha-ras mutations in virgin female F344 rat mammary glands. Two groups of 15 rats each were fed isocaloric diets containing either 23% w/w corn oil or corn oil plus menhaden oil (1:1) at starting 14 d before NMU administration (day 50 of age) and continuing for 13 wk. Mammary gland samples were taken serially at 3, 5, 9, and 13 wk post-NMU treatment. Total cellular DNA was isolated and analyzed by a newly devised enriched amplification procedure that involves predigestion of normal Ha-ras alleles at codon 12, amplification of the mutant alleles, and restriction fragment length polymorphism analysis. Selective amplification enabled the detection of Ha-ras mutations as early as 3 wk post-NMU treatment. Approximately 40-50% of all glands and 75% of all rats tested had the Ha-ras codon 12 mutation. No significant differences were found between the two dietary groups at any time point, indicating that the mammary tumor-inhibiting effect of n-3 PUFA is probably not exerted at the level of the Ha-ras activation step in NMU tumorigenesis.
Ronai
Z
Z
Molecular Carcinogenesis Program, American Health Foundation, Valhalla, New York 10595.
Lau
Y Y
YY
Cohen
L A
LA
D000818:Animals; D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004041:Dietary Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005784:Gene Amplification; D011905:Genes, ras / Q000187:drug effects*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008770:Methylnitrosourea / Q000633:toxicity*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D015345:Oligonucleotide Probes; D051381:Rats; D011916:Rats, Inbred F344
D003062:Codon; D004273:DNA, Neoplasm; D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D015345:Oligonucleotide Probes; D008770:Methylnitrosourea; D004247:DNA