Enhanced spontaneous and aflatoxin-induced liver tumorigenesis in xeroderma pigmentosum group A gene-deficient mice.
Xeroderma pigmentosum (XP) is an autosomal recessive hereditary disease featuring defective nucleotide excision repair (NER). XP patients are highly sensitive to sunlight and develop skin cancer at an early age. While the fact that XP patients have a large increase in mortality from skin cancers has been extensively documented, the relation between XP and internal tumors has received little attention. We therefore analyzed development of spontaneous and aflatoxin B(1) (AFB(1))-induced liver tumors in XPA-deficient congenic mice, originally created by repeated back-crosses with inbred C3H/HeN mice. Spontaneous liver tumors were assessed at the age of 16 months in two separate experiments using F5 and F10 lines. The incidence of and average number of spontaneous tumors per mouse were significantly higher in XPA-/- than in XPA+/+ and +/- mice. Similarly, F10 XPA-/- mice receiving i.p. injection of 0.6 or 1.5 mg/kg b.w. AFB(1) at 7 days of age demonstrated more liver tumors than their heterozygous or homozygous positive counterparts when examined at month 11. These results demonstrate that XPA-deficient mice have increased susceptibility to both spontaneous liver tumor development and AFB(1)-induced hepatocarcinogenesis.
Takahashi
Yoshihisa
Y
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Nakatsuru
Yoko
Y
Zhang
Shaomin
S
Shimizu
Yasuhito
Y
Kume
Haruki
H
Tanaka
Kiyoji
K
Ide
Fumio
F
Ishikawa
Takatoshi
T
D016604:Aflatoxin B1; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D022781:Hepatocytes / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D008113:Liver Neoplasms / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D016196:S Phase; D012878:Skin Neoplasms / Q000235:genetics; D013997:Time Factors; D051760:Xeroderma Pigmentosum Group A Protein
D002273:Carcinogens; D004268:DNA-Binding Proteins; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D016604:Aflatoxin B1