Spontaneous liver tumors and Benzo[a]pyrene-induced lymphomas in XPA-deficient mice

✍ Scribed by Annemieke de Vries; Conny T. M. van Oostrom; Paul M. Dortant; Rudolf B. Beems; Coen F. van Kreijl; Peter J. A. Capel; Harry van Steeg

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 236 KB
• Volume: 19
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199705)19:1<46::aid-mc7>3.0.co;2-l

✦ Synopsis

Defects in the xeroderma pigmentosum complementation group A-correcting (XPA) gene, which encodes a component of the nucleotide excision repair (NER) pathway, are associated with the cancer-prone human disease xeroderma pigmentosum. We previously generated mice lacking the XPA gene, which develop normally but are highly sensitive to ultraviolet-B and 7,12-dimethylbenz[a]anthracene-induced skin tumors. Here we report that XPA-deficient mice spontaneously developed hepatocellular adenomas at a low frequency as they aged. Furthermore, oral treatment of XPA-deficient mice with the carcinogen benzo[a]pyrene (B[a]P) resulted in the induction of mainly lymphomas. These tumors appeared earlier and with a higher incidence than in B[a]P-treated wild-type and heterozygous mice. Our results show for the first time that XPA-deficient mice also displayed an increased sensitivity to developing tumors other than tumors of the skin.