First Author | Xia Q | Year | 1998 |
Journal | Cancer Lett | Volume | 123 |
Issue | 1 | Pages | 21-5 |
PubMed ID | 9461013 | Mgi Jnum | J:45829 |
Mgi Id | MGI:1196168 | Doi | 10.1016/s0304-3835(97)00366-2 |
Citation | Xia Q, et al. (1998) Liver tumors induced in B6C3F1 mice by 7-chlorobenz[a]anthracene and 7-bromobenz [a]anthracene contain K-ras protooncogene mutations. Cancer Lett 123(1):21-5 |
abstractText | We previously examined the tumorigenicity of 7-chlorobenz[a]anthracene (7-Cl-BA) and 7-bromobenz[a]anthracene (7-Br-BA) in the neonatal mouse bioassay and found that 7-Cl-BA and 7-Br-BA induced hepatocellular adenoma in 92 and 96% of the mice and hepatocellular carcinoma in 100 and 83% of the mice, respectively. In the present study, mRNA was isolated from each of the liver tumors induced by the two compounds and reverse-transcribed to cDNA. Portions of the K- and H-ras oncogene coding sequences were then amplified and analyzed for DNA sequence alterations. Eighty-three percent (20/24) of 7-Cl-BA-induced and 91% (20/22) of 7-Br-BA-induced liver tumors had activated ras protooncogenes. In contrast to the general finding of H-ras mutations in B6C3F1 mouse liver tumors, both compounds had 95% (19/20) of the mutations located at the first base of K-ras codon 13, resulting in a pattern of GGC --> CGC. Thus, our results demonstrate that 7-Cl-BA and 7-Br-BA induce a unique type of ras (K-ras) oncogene activation in liver tumors of B6C3F1 mice. |