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Goodrow TL , Nichols WW , Storer RD , Anderson MW , Maronpot RR
Activation of H-Ras Is Prevalent in 1,3-Butadiene-Induced and Spontaneously Occurring Murine Harderian-Gland Tumors
Carcinogenesis. 1994 Nov;15(11) :2665-2667
PMID: ISI:A1994PT04100042   
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Treatment of B6C3F(1) mice with concentrations of 62.5-625 p.p.m. 1,3-butadiene by inhalation for up to 2 years causes a significantly increased incidence of Harderian gland (HG) neoplasms over untreated controls (Melnick,R., Huff, J., Chou, B.J. and Miller, R.A. Cancer Res., 50, 6592-6599, 1990). Since a specific K-r as mutation (codon 13 GGC-->CGC) had previously been described in lung and liver tumors from 1,3-butadiene- treated B6C3F(1) mice, we analyzed 23 adenomas and six adenocarcinomas of the HG from mice exposed to 1,3-butadiene for this mutation and mutations in the H-ms gene. We also examined ras activation in 16 spontaneously occurring HG adenomas and one adenocarcinoma. DNA samples were prepared from paraffin-embedded tissues and analyzed by PCR followed by direct sequencing methods. Only one 1,3-butadiene-induced HG tumor contained the K-ras codon 13 mutation previously detected in lung and liver tumors. However, 16/29 HG tumors from the treated B6C3F(1) mice contained H-ms codon 61 mutations. The mutations detected were: 12 CAA-->CGA transitions, two CAA-- >CTA and two CAA-->AAA transversions. Eleven of 17 spontaneous HG tumors contained mutations in H-ras codon 61: five CAA-->CGA transitions, two CAA-->CTA transversions and four CAA-->AAA transversions. While the spectrum of ras mutations did not differ between the spontaneously occurring and chemically induced tumors, these data indicate that activation of H-ras contributes to the process of HG tumorigenesis in both groups of these neoplasms.