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Environ Mol Mutagen 2013 Oct;54(8):659-67

ACB-PCR measurement of spontaneous and furan-induced H-ras Codon 61 CAA to CTA and CAA to AAA mutation in B6C3F1 mouse liver.

Banda M, Recio L, Parsons BL

Abstract

Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H-ras codon 61 CAA to AAA mutation increased in furan-treated mice. Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to quantify early, carcinogen-induced increases in tumor-associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre-existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and CAA to AAA mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H-ras codon 61 CTA or AAA mutant fraction (MF) greater than 10-5 . Several furan-treated mice had H-ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically-significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H-ras mutant cells. Environ. Mol. Mutagen., 2013. (c) 2013 Wiley Periodicals, Inc.


Category: Journal Article
PubMed ID: #24038307 DOI: 10.1002/em.21808
Includes FDA Authors from Scientific Area(s): Toxicological Research
Entry Created: 2013-09-17 Entry Last Modified: 2013-11-02
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