Journal Article

Enhanced spontaneous and aflatoxin-induced liver tumorigenesis in xeroderma pigmentosum group A gene-deficient mice

Yoshihisa Takahashi, Yoko Nakatsuru, Shaomin Zhang, Yasuhito Shimizu, Haruki Kume, Kiyoji Tanaka, Fumio Ide and Takatoshi Ishikawa

in Carcinogenesis

Volume 23, issue 4, pages 627-633
Published in print April 2002 | ISSN: 0143-3334
Published online April 2002 | e-ISSN: 1460-2180 | DOI:
Enhanced spontaneous and aflatoxin-induced liver tumorigenesis in xeroderma pigmentosum group A gene-deficient mice

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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 B1 (AFB1)-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. AFB1 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 AFB1-induced hepatocarcinogenesis.

Keywords: AFB1, aflatoxin B1; BrdU, 5-bromo-2′-deoxyuridine; DMBA, 9,10-dimethyl-1,2-benzanthracene; DMSO, dimethyl sulfoxide; NER, nucleotide excision repair; 8-oxo-dGTP, 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate; PCR, polymerase chain reaction; UV, ultraviolet; XP, xeroderma pigmentosum; XPA, xeroderma pigmentosum group A.

Journal Article.  5292 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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