| Abstrakt: |
Treatment of B6C3F 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. , 50, 6592–6599, 1990). Since a specific K- mutation (codon 13 GGC→CGC) had previously been described in lung and liver tumors from 1, 3-butadiene-treated B6C3F mice, we analyzed 23 adenomas and sis adenocarcinomas of the HG from mice exposed to 1,3-butadiene for this mutation and mutations in the H- gene. We also examined 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- codon 13 mutation previously detected in lung and liver tumors. However, 16/29 HG tumors from the treated B6C3F mice contained H- 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- codon 61: five CA→CGA transitions, two CAA→CTA transversions and four CAA→AAA transversions. While the spectrum of mutations did not differ between the spontaneously occurring and chemically induced tumors, these data indicate that activation of H- contributes to the process of HG tumorigenesis in both groups of these neoplasms. [ABSTRACT FROM PUBLISHER] |
