Journal Article

Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis

Fumio Ide, Hideaki Oda, Yoko Nakatsuru, Kaoru Kusama, Hideaki Sakashita, Kiyoji Tanaka and Takatoshi Ishikawa

in Carcinogenesis

Volume 22, issue 4, pages 567-572
Published in print April 2001 | ISSN: 0143-3334
Published online April 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.4.567
Xeroderma pigmentosum group A gene action as a protection factor against 4-nitroquinoline 1-oxide-induced tongue carcinogenesis

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To test the hypothesis that nucleotide excision repair (NER) plays a protective role in chemical carcinogenesis in internal organs, xeroderma pigmentosum group A gene-deficient (XPA–/–) mice, heterozygous (XPA+/–) and wild-type (XPA+/+) mice were orally administered 0.001% 4-nitroquinoline 1-oxide (4NQO) in their drinking water and compared. After 50 weeks of 4NQO exposure, tongue squamous cell carcinomas (SCCs) occurred in XPA–/– mice only, no tumors being observed in XPA+/– and XPA+/+ animals. Of the XPA–/– mice 86% had tumors and 100% demonstrated multiple foci of dysplastic epithelium in the tongue. Accumulation of p53 protein was immunohistochemically detected in 56% of the SCCs. Mutational analysis of the p53 gene (exons 4–10) in carcinoma DNA revealed missense mutations in exons 5 and 9 in four of 20 samples. Our results clearly demonstrate that the NER gene XPA acts as a defensive factor against 4NQO-induced tongue carcinogenesis in vivo.

Keywords: NER, nucleotide excision repair; 4NQO, 4-nitroquinoline 1-oxide; SCC, squamous cell carcinoma; XP, xeroderma pigmentosum; XPA, XP group A; XPC, XP group C.

Journal Article.  4039 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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