Abstract:
: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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Ide F,Oda H,Nakatsuru Y,Kusama K,Sakashita H,Tanaka K,Ishikawa Tdoi
10.1093/carcin/22.4.567keywords:
subject
Has Abstractpub_date
2001-04-01 00:00:00pages
567-72issue
4eissn
0143-3334issn
1460-2180journal_volume
22pub_type
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