Mice deficient in the nucleotide excision repair gene XPA have elevated sensitivity to benzo[a]pyrene induction of lung tumors.
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.
Ide
F
F
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Iida
N
N
Nakatsuru
Y
Y
Oda
H
H
Tanaka
K
K
Ishikawa
T
T
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D014983:Xeroderma Pigmentosum / Q000235:genetics; D051760:Xeroderma Pigmentosum Group A Protein
D002273:Carcinogens; D004268:DNA-Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D001564:Benzo(a)pyrene