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Advances in Brief

Immunogenetic Influences on the Initiation Stage of the Cutaneous Chemical Carcinogenesis Pathway

Craig A. Elmets, Syed I. A. Zaidi, David R. Bickers and Hasan Mukhtar
Craig A. Elmets
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Syed I. A. Zaidi
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David R. Bickers
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Hasan Mukhtar
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DOI:  Published November 1992
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Abstract

While it is generally agreed that environmental exposure to solar radiation and to certain classes of chemicals are the major causes of nonmelanoma skin cancer, it is also believed that genetic polymorphisms regulating immunological responses are important determinants of individual susceptibility to skin cancer. However, little is known about their interactions with the chemical carcinogenesis pathway prior to the actual development of tumors. This issue was examined by comparing susceptibility to skin cancer in C3H/HeN and C3H/HeJ mice, two strains that differ only at the lipopolysaccharide genetic locus, which serves as a regulator of a number of immunological activities. When subjected to a two-stage cutaneous tumorigenesis protocol, C3H/HeJ mice, which have a mutation at the lipopolysaccharide genetic locus that renders them deficient in their capacity to produce cytokines and to activate macrophages, developed nearly three times as many tumors as did C3H/HeN mice, which do not have this mutation. Epidermal DNA binding of 7,12-[3H]dimethylbenz(a)anthracene, an index of tumor initiation, was also significantly greater in C3H/HeJ than in C3H/HeN mice. Immunological activities regulated by the lipopolysaccharide genetic locus thus confer resistance to DMBA-induced cutaneous tumorigenesis in mice and are associated with changes that occur early in the tumorigenesis pathway, prior to the development of tumors.

Footnotes

  • ↵1 Supported by NIH Grants AR32593, CA48763, CA51802, ES1900, and P30-AR39750 and by research funds from the Department of Veterans Affairs.

  • ↵2 Recipient of NIH Research Career Development Award AR01765. To whom requests for reprints should be addressed, at Department of Dermatology, University Hospitals of Cleveland, 2074 Abington Road, Cleveland, OH 44106.

  • Received August 11, 1992.
  • Accepted September 15, 1992.
  • ©1992 American Association for Cancer Research.
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November 1992
Volume 52, Issue 21
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Immunogenetic Influences on the Initiation Stage of the Cutaneous Chemical Carcinogenesis Pathway
Craig A. Elmets, Syed I. A. Zaidi, David R. Bickers and Hasan Mukhtar
Cancer Res November 1 1992 (52) (21) 6106-6109;

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Immunogenetic Influences on the Initiation Stage of the Cutaneous Chemical Carcinogenesis Pathway
Craig A. Elmets, Syed I. A. Zaidi, David R. Bickers and Hasan Mukhtar
Cancer Res November 1 1992 (52) (21) 6106-6109;
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