The effect of humoral immunity against adducted benzo[a]pyrene on DNA damage elicited by acute carcinogen exposure in Swiss mice.
Immunoglobulins G (lgG) specific for benzo[a]pyrene-DNA adducts were elicited in Swiss mice by repeated subcutaneous injections of a high molecular weight benzo[a]pyrene-DNA conjugate-adjuvant mix. The immunization procedure resulted in the production of specific antibodies against adducted benzo[a]pyrene B[a]P in all treated animals. One week after completion of the immunization procedure, groups of ten immunized and ten non immunized female mice were treated by single intraperitoneal injection with two different doses of B[a]P. The mice were sacrificed 48 hours after treatment, and both liver and bone marrow cells were isolated for subsequent determinations of DNA binding and micronucleus induction, respectively. Covalent benzo[a]pyrene adducts in liver DNA were detected by competitive ELISA and the incidence of micronucleated polychromatic erythrocytes was evaluated by scoring one thousand cells per animal. The determination of DNA adducts in liver revealed significantly (p < 0.05) lower levels of B[a]P adducts in immunized mice compared to non-immunized animals at both doses, whereas no significant difference was observed between controls. Administration of benzo[a]pyrene produced moderate, dose-related increases in the incidence of micronucleated polychromatic erythrocytes in all treated groups, with no significant difference between immunized and non-immunized mice. The decrease of covalent DNA adducts in the liver of immunized mice suggests that the specific humoral immunity elicited by repeated carcinogen exposure may act as a relevant modulating factor in chemical carcinogenesis.
Galati
R
R
Laboratory of Biochemistry, Regina Elena Institute for Cancer Research, Rome, Italy.
Crebelli
R
R
Zijno
A
A
Conti
L
L
Falasca
G
G
Verdina
A
A
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D002273:Carcinogens / Q000494:pharmacology; D018736:DNA Adducts / Q000276:immunology*; D004249:DNA Damage / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000276:immunology; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000276:immunology; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000276:immunology
D002273:Carcinogens; D018736:DNA Adducts; D001564:Benzo(a)pyrene