Spontaneous liver tumors and benzo[a]pyrene-induced lymphomas in XPA-deficient mice.
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.
de Vries
A
A
Department of Immunology, University of Utrecht, The Netherlands.
van Oostrom
C T
CT
Dortant
P M
PM
Beems
R B
RB
van Kreijl
C F
CF
Capel
P J
PJ
van Steeg
H
H
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002470:Cell Survival / Q000502:physiology; D003043:Cocarcinogenesis; D004260:DNA Repair / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000235:genetics*; D008223:Lymphoma / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D002273:Carcinogens; D001564:Benzo(a)pyrene