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

David L. Cheo, Dennis K. Burns, Lisiane B. Meira, Jean Francois Houle, Errol C. Friedberg

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Abstract

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(-/-) Trp53(-/-) double mutant mice compared with XPC(+/+) Trp53(-/-) mice.

Original languageEnglish (US)
Pages (from-to)771-775
Number of pages5
JournalCancer Research
Volume59
Issue number4
StatePublished - Feb 15 1999

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2-Acetylaminofluorene
Xeroderma Pigmentosum
Testicular Neoplasms
Liver Neoplasms
Lung Neoplasms
Genes
DNA Repair
Neoplasms
Radiation-Induced Neoplasms
Environmental Carcinogens
Liver
Incidence
Skin Neoplasms
Carcinogenesis
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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title = "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",
abstract = "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(-/-) Trp53(-/-) double mutant mice compared with XPC(+/+) Trp53(-/-) mice.",
author = "Cheo, {David L.} and Burns, {Dennis K.} and Meira, {Lisiane B.} and Houle, {Jean Francois} and Friedberg, {Errol C.}",
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AU - Cheo, David L.

AU - Burns, Dennis K.

AU - Meira, Lisiane B.

AU - Houle, Jean Francois

AU - Friedberg, Errol C.

PY - 1999/2/15

Y1 - 1999/2/15

N2 - 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(-/-) Trp53(-/-) double mutant mice compared with XPC(+/+) Trp53(-/-) mice.

AB - 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(-/-) Trp53(-/-) double mutant mice compared with XPC(+/+) Trp53(-/-) mice.

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