Absence of p53 mutations and various frequencies of Ki-ras exon 1 mutations in rat hepatic tumors induced by different carcinogens
- PMID: 8185829
- DOI: 10.1002/mc.2940100108
Absence of p53 mutations and various frequencies of Ki-ras exon 1 mutations in rat hepatic tumors induced by different carcinogens
Abstract
Mutations of p53 and Ki-ras exon 1 were investigated in rat hepatic lesions induced by four kinds of hepatocarcinogenic protocols: continuous feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), daily intraperitoneal injection of aflatoxin B1 (AFB1), and the Solt and Farber regimen (Nature 236:701-703, 1976), in which diethylnitrosamine (DEN) or nitrosomethylurea (NMU) was used as initiating agents. DNA from microdissected tissue sections was amplified by the polymerase chain reaction (PCR) directly using primers for p53 exons 5-8 and Ki-ras exon 1 and analyzed for mutations by denaturing gradient gel electrophoresis (DGGE) or constant denaturant gel electrophoresis (CDGE). One or both of the p53 PCR primers were located within introns to prevent amplifying the p53 processed pseudogenes. In a total of 59 hepatocellular carcinomas (HCCs), no p53 aberrations were detected, indicating that p53 mutations are not very important in rat hepatic carcinogenesis. On the other hand, Ki-ras codon 12 mutations were found at low frequency in HCCs, hyperplastic foci, and cholangiofibroses induced by 3'-Me-DAB and by AFB1 but not in the lesions induced by the Solt and Farber regimen. Although Ki-ras codon 12 mutations are generally infrequent in rat hepatic tumors, their incidence thus appears to vary depending on the carcinogen used for their induction.
Similar articles
-
Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat.Jpn J Cancer Res. 1997 Feb;88(2):129-36. doi: 10.1111/j.1349-7006.1997.tb00357.x. Jpn J Cancer Res. 1997. PMID: 9119740 Free PMC article.
-
Detection of p53 gene mutations in rat hepatocellular carcinoma cell lines by denaturing gradient gel electrophoresis.Mol Carcinog. 1993;7(4):257-62. doi: 10.1002/mc.2940070408. Mol Carcinog. 1993. PMID: 8352884
-
Activation of the c-Ki-ras oncogene in aflatoxin B1-induced hepatocellular carcinoma and adenoma in the rat: detection by denaturing gradient gel electrophoresis.Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2045-9. doi: 10.1073/pnas.90.5.2045. Proc Natl Acad Sci U S A. 1993. PMID: 8446626 Free PMC article.
-
Mutagenesis of the H-ras protooncogene and the p53 tumor suppressor gene.Cancer Res. 1994 Apr 1;54(7 Suppl):1934s-1938s. Cancer Res. 1994. PMID: 7907948 Review.
-
Mutations of the p53 tumor suppressor gene and ras oncogenes in aflatoxin hepatocarcinogenesis.Mutat Res. 1996 Oct;366(1):23-44. doi: 10.1016/s0165-1110(96)90005-6. Mutat Res. 1996. PMID: 8921985 Review.
Cited by
-
Mode of action-based risk assessment of genotoxic carcinogens.Arch Toxicol. 2020 Jun;94(6):1787-1877. doi: 10.1007/s00204-020-02733-2. Epub 2020 Jun 15. Arch Toxicol. 2020. PMID: 32542409 Free PMC article. Review.
-
Alterations in the K-ras and p53 genes in rat lung tumors.Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):901-6. doi: 10.1289/ehp.97105s4901. Environ Health Perspect. 1997. PMID: 9255578 Free PMC article.
-
Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat.Jpn J Cancer Res. 1997 Feb;88(2):129-36. doi: 10.1111/j.1349-7006.1997.tb00357.x. Jpn J Cancer Res. 1997. PMID: 9119740 Free PMC article.
-
Absence of ras mutations and low incidence of p53 mutations in renal cell carcinomas induced by ferric nitrilotriacetate.Jpn J Cancer Res. 1995 Dec;86(12):1143-9. doi: 10.1111/j.1349-7006.1995.tb03307.x. Jpn J Cancer Res. 1995. PMID: 8636002 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous
