+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Infrequent Ha-ras mutations and absence of Ki-ras, N-ras, and p53 mutations in 4-nitroquinoline 1-oxide-induced rat oral lesions



Infrequent Ha-ras mutations and absence of Ki-ras, N-ras, and p53 mutations in 4-nitroquinoline 1-oxide-induced rat oral lesions



Molecular Carcinogenesis. 14(4): 294-298



The alkylating agent 4-nitroquinoline 1-oxide (4-NQO) is a powerful carcinogen and induces squamous cell hyperplasia, squamous cell dysplasia, papilloma, and squamous cell carcinoma (SCC) in rat oral epithelia. Oral cancers induced by a single application of 4-NQO develop through a multistage process in a way similar to the development of this cancer in humans. In this study, mutations in exons 1 and 2 of Ki-ras, N-ras, and Ha-ras and exons 4-7 of p53 were examined by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, followed by PCR-direct sequencing for the confirmation of mutations. Samples for the mutation analysis were obtained from dysplasias, papillomas, and SCCs on the tongue epithelia induced in F344 rats by adding 4-NQO (20 ppm) to their drinking water for 8 wk. The Ha-ras mutations (61A fwdarw T transversions in the second position) were found in five of 29 (17%) samples (one dysplasia and four SCCs). However, no mutations were detected in either Ki-ras, N-ras, or p53 under two different conditions of PCR-SSCP analysis. We suggest that some neoplasms in oral carcinogenesis induced by 4-NQO may involve Ha-ras mutations but not mutations in Ki-ras, N-ras, or p53. The 4-NQO-induced rat oral carcinogenesis model may provide a system for evaluation of the mechanisms of multistage oral carcinogenesis associated with Ha-ras mutation without Ki-ras, N-ras, or p53 mutation.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008873618

Download citation: RISBibTeXText

PMID: 8519419

DOI: 10.1002/mc.2940140410


Related references

4-Nitroquinoline-1-oxide induced oral cavity Ha-ras mutations lead to loss of heterozygosity , gene amplification, and genomic instability during neoplastic transformation. Proceedings of the American Association for Cancer Research Annual Meeting 36: 542, 1995

Characterization of mutations in 4-nitroquinoline-1-oxide -transformed, cultured murine oral keratinocytes. Proceedings of the American Association for Cancer Research Annual Meeting 38: 125, 1997

Suppressor mutations induced by 4-nitroquinoline 1-oxide and 4-hydroxyaminoquinoline 1-oxide in Escherichia coli. Gan 63(5): 511-515, 1972

Harvey ras (H-ras) point mutations are induced by 4-nitroquinoline-1-oxide in murine oral squamous epithelia, while squamous cell carcinomas and loss of heterozygosity occur without additional exposure. Cancer Research 54(20): 5310-5317, 1994

Molecular nature of the direct mutations induced by 4-nitro-quinoline-N-oxide and 3-methyl-4-nitroquinoline-N-oxide in the ADE2 gene of Saccharomyces cerevisiae. Genetika 21(6): 914-918, 1985

The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas. International Journal of Oncology 16(3): 585-590, 2000

Ki-ras gene mutations and absence of p53 gene mutations in spontaneous and urethane-induced early lung lesions in CBA/J mice. Molecular Carcinogenesis. 21(4): 251-260, Il, 1998

No mutations found in exon 2 of gene p16CDKN2A during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide. Journal of Molecular Histology 40(1): 71-76, 2009

4-Nitroquinoline 1-oxide-induced deletion mutations in Escherichia coli strains with different DNA repair capacities. Mutation Research 22(1): 81-83, 1974

Infrequent Ki-ras and an absence of p53 mutations in hepatocellular carcinomas induced by a choline deficient L-amino acid defined diet in rats. Cancer Letters. 108(1): 137-141, 1996

Analysis of 4-nitroquinoline-1-oxide induced mutations at the hprt locus in mammalian cells: possible involvement of preferential DNA repair. Mutagenesis 9(1): 67-72, 1994

Novel mutations of the HRAS gene and absence of hotspot mutations of the BRAF genes in oral squamous cell carcinoma in a Greek population. Oncology Reports 27(5): 1555-1560, 2012

Modifying effect of interferon on the formation of structural chromosome mutations and sister chromatid exchanges induced by fast neutrons and 4-nitroquinoline-1'-oxide in human leukocytes in vitro. Radiobiologiia 22(6): 769-775, 1982

Absence of K-ras mutations in CI-945-induced pancreatic lesions in male rats. Proceedings of the American Association for Cancer Research Annual Meeting 34: 99, 1993

Absence of p53 mutations and various frequencies of Ki-ras exon 1 mutations in rat hepatic tumors induced by different carcinogens. Molecular Carcinogenesis. 10(1): 45-51, 1994