Effects of specific humoral immunity on DNA-adduct formation in Swiss mice treated with benzo[alpha]pyrene.
In order to study the effect of possible modulating factors on DNA-binding carcinogens, we investigated the role of specific immune response on racemic 7,t-8-dihydroxy-t-9,10-epoxy-7,8,9, 10-tetrahydro-benzo[a]pyrene ((+/-)-anti BPDE)-DNA (BPDE-DNA) adduct formation. Anti BPDE Immunoglobulin G (IgG) were elicited in Swiss mice before subsequent carcinogen administration. The immunization schedule consisted of four weekly subcutaneous injections of both (+/-)-anti BPDE-gelatin (BPDE-Gel) and DNA (BPDE-DNA) conjugate, followed by a final immunogen injection 14 days later. The immunization procedure resulted in the production of specific anti-BPDE antibodies in all treated animals. One week after the end of the immunization procedure, both groups of immunized and non immunized mice were treated with different doses of B[a]P (25-50-100-200 mg B[a]P/Kg body weight) by intraperitoneal injection. Seven days after treatment, the mice were sacrificed. Adduct levels were detected by competitive ELISA by using optimal conditions established in our laboratory and highly specific and sensitive IgG anti BPDE-DNA induced in rabbit. The determination of DNA adducts in liver revealed significantly lower B[a]P adduct levels in liver of immunized mice with respect to non-immunized animals. This result confirms those obtained for 2-acetylaminofluorene (2-AAF) in a previous work: the specific humoral immunity elicited by repeated carcinogen exposure may be able to modulate the genotoxic effect induced by subsequent carcinogen administration.
Galati
R
R
Laboratory of Biochemistry, Regina Elena Institute for Cancer Research, Rome, Italy.
Falasca
G
G
Verdina
A
A
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens; D018736:DNA Adducts; D004249:DNA Damage / Q000276:immunology*; D005260:Female; D007114:Immunization; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D011817:Rabbits
D002273:Carcinogens; D018736:DNA Adducts; D007074:Immunoglobulin G; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide