Induction of humoral immunity toward 2-acetylaminofluorene in mice: modulation of DNA binding after 4 weeks dietary exposure to the carcinogen.
In order to investigate the modulatory effect of the immune response induced by recurrent carcinogen exposure, anti-2-acetylaminofluorene (anti-2-AAF) IgG were elicited in Swiss mice before subsequent carcinogen administration. The immunization schedule consisted of three weekly i.p. injections of 2-acetylaminofluorene (2-AAF)-gelatin conjugate, followed by a final immunogen injection 14 days later. At the end of treatment, the presence of specific anti-2-AAF antibodies in blood serum of all immunized animals was demonstrated. The immunization procedure did not affect liver metabolic activities, as evaluated using liver homogenates for the exogenous activation of 2-AAF to mutagen. After immunization, mice were fed 2-AAF pelleted in the diet at 50 and 150 p.p.m. for 4 weeks and killed at the end of treatment. The determination of DNA adducts by ELISA in liver and spleen of treated animals revealed significantly (P < 0.01-0.001) lower 2-AAF adduct levels in both tissues of immunized mice with respect to non-immunized animals (both naive and pretreated with the adjuvant alone). This result suggests that the specific humoral immunity elicited by repeated carcinogen exposure may be able to modulate the genotoxic effect induced by subsequent carcinogen administration.
Verdina
A
A
Istituto Regina Elena, Rome, Italy.
Zito
R
R
Cortese
G
G
Leopardi
P
P
Marcon
F
F
Zijno
A
A
Crebelli
R
R
D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005247:Feeding Behavior / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D012486:Salmonella typhimurium / Q000235:genetics; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D004247:DNA; D015073:2-Acetylaminofluorene