Modulation of DNA binding in vivo by specific humoral immunological response: a novel host factor in environmental carcinogenesis?
To investigate the possible modulatory effect of the immune response induced by recurrent carcinogen exposure, a specific humoral immune response toward 2-acetylaminofluorene (2-AAF) was elicited in Swiss mice with repeated intraperitoneal injections of a 2-AAF-gelatin conjugate. The immunization procedure resulted in the production of specific anti-2-AAF antibodies in all treated animals. Groups of immunized and nonimmunized mice were subsequently fed 2-AAF pelleted in the diet at 50 and 150 ppm for 4 weeks. At the end of 2-AAF administration, animals were sacrificed and the content of 2-AAF-adducts in liver DNA was determined by enzyme-linked immunoadsorbent assay using a polyclonal rabbit antiserum. The comparison of the adducts levels in immunized and nonimmunized mice (receiving either the vehicle or the adjuvant alone during pretreatment) demonstrates a highly significant (p < 0.001) difference among groups, with far lower adduct levels in immunized animals. No significant difference in food consumption or liver metabolic activities was observed among experimental groups, suggesting the absence of external bias. The mechanism underlying the result observed is not yet clear; however, the experimental data strongly suggest that the specific immunological response induced by recurrent carcinogen exposure may exert a modulatory effect and act as a relevant host factor in chemical carcinogenesis.
Verdina
A
A
Centro Ricerche Sperimentali, Istituto Regina Elena, Rome, Italy.
Zito
R
R
Cortese
G
G
Zijno
A
A
Crebelli
R
R
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000917:Antibody Formation; D002274:Carcinogens, Environmental / Q000633:toxicity; D004247:DNA / Q000187:drug effects*; D018736:DNA Adducts / Q000032:analysis; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D011817:Rabbits
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D007074:Immunoglobulin G; D004247:DNA; D015073:2-Acetylaminofluorene