Mutational inactivation of the xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/- mice.
Mice that are genetically engineered to mimic the human hereditary cancer-prone DNA repair-defective disease xeroderma pigmentosum (XP) are highly predisposed to UV radiation-induced skin cancer. It is not clear, however, whether XP mice or humans are predisposed to cancers in other tissues associated with exposure to environmental carcinogens. To test the importance of nucleotide excision repair in protection against chemical carcinogenesis in internal organs, we treated XPC mutant (XPC-/-) mice with 2-acetylaminofluorene and NOH-2-acetylaminofluorene. We observed a significantly higher incidence of chemically induced liver and lung tumors in XPC-/- mice compared with normal and heterozygous littermates In addition, the progression of liver tumors in XPC-/- Trp53+/- mice is accelerated compared with XPC-/- Trp53+/+ animals. Finally, we demonstrate a higher incidence of spontaneous testicular tumors in XPC-/- TrpS3-/- double mutant mice compared with XPC+/+ Trp53-/- mice.
Cheo
D L
DL
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
Burns
D K
DK
Meira
L B
LB
Houle
J F
JF
Friedberg
E C
EC
D015073:2-Acetylaminofluorene / Q000633:toxicity*; D000818:Animals; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D013736:Testicular Neoplasms / Q000209:etiology*; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D015073:2-Acetylaminofluorene