Abstract:
:Polyaromatic hydrocarbons are ubiquitous environmental chemicals that are important mutagens and carcinogens. The purpose of this study was to determine whether genes within the major histocompatibility complex (MHC) influence their biological activities. Cell-mediated immunity to dimethylbenz(a)anthracene (DMBA) was investigated in congenic strains of mice. On three different backgrounds, H-2(k) and H-2(a) haplotype mice developed significantly greater contact-hypersensitivity responses to DMBA than H-2(b), H-2(d), and H-2(s) mice. In B10.A(R1) mice, which are Kk and Id, a vigorous contact-hypersensitivity response was present, indicating that the response was governed by class I, rather than class II, MHC genes. C3H/HeN (H-2(k)) and C3H.SW (H-2(s)) strains were also compared for the development of skin tumors and the persistence of DMBA-DNA adducts. When subjected to a DMBA initiation, phorbol 12-tetradecanoate 13-acetate (TPA)-promotion skin-tumorigenesis protocol, C3H/HeN mice, (which develop cell-mediated immunity to DMBA) were found to have significantly fewer tumors than C3H.SW mice (a strain that failed to develop a cell-mediated immune response to DMBA). DMBA-DNA adducts were removed more rapidly in C3H/HeN than in C3H.SW mice. The results indicate that genes within the MHC play an important role in several of the biological activities of carcinogenic polyaromatic hydrocarbons. The observations are consistent with the hypothesis that cell-mediated immunity to chemical carcinogens serves to protect individuals by removing mutant cells before they can evolve into clinically apparent neoplasms.
journal_name
Proc Natl Acad Sci U S Aauthors
Elmets CA,Athar M,Tubesing KA,Rothaupt D,Xu H,Mukhtar Hdoi
10.1073/pnas.95.25.14915subject
Has Abstractpub_date
1998-12-08 00:00:00pages
14915-9issue
25eissn
0027-8424issn
1091-6490journal_volume
95pub_type
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