Carcinogenesis, Vol. 21, No. 6, 1263-1265,
June 2000
© 2000 Oxford University Press
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Mice deficient in the nucleotide excision repair gene XPA have elevated sensitivity to benzo[a]pyrene induction of lung tumors
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 and
1 Division of Cellular Genetics, Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565, Japan
This study is focused on chemical induction of lung tumors in xeroderma pigmentosum group A gene (XPA)-deficient mice to clarify the role of nucleotide excision repair (NER) in internal organs. Six-week-old female XPA–/–, XPA+/– and XPA+/+ mice were instilled intratracheally with benzo[a] pyrene (B[a]P). A total of 68 surviving XPA mice treated with B[a]P were examined at month 16. The pulmonary adenoma incidence in XPA–/– mice was significantly higher than that in XPA+/+ mice (71 versus 35%). Similarly, tumor multiplicity was elevated and, in addition, only XPA–/– mice had lung carcinomas. These results provide the first evidence that a deficiency in the NER gene XPA leads to enhanced tumorigenesis in the lung after exposure to B[a]P.
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