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,vith 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.