Peroral administration of specific antibody enhances carcinogen excretion.
Ingested carcinogens may exert effects directly on the gastrointestinal epithelium or after absorption and transport to other tissues. To determine the effect of anti-carcinogen antibody ingestion on dietary carcinogen excretion, a mixture of specific IgA or IgG and the model carcinogen 125I-N-2-(4-hydroxyphenyl-acetamido) fluorene (125I-pHP-AAF) was perorally administered to mice. These mice excreted more total and antibody-bound radiotracer in feces compared with controls given a similar mixture containing nonspecific antibody. In addition, urinary radiotracer excretion was reduced by 96% in specific-antibody dosed mice, indicating reduced gastrointestinal absorption of 125I-pHP-AAF. Reduced radiotracer absorption was also reflected by a 56% reduction in radiotracer content in tissues from mice receiving specific antibody. Other mice received peroral IgA before i.p. injection of 125I-PH-AAF. Specific antibody treatment consistently increased intraluminal radiotracer sequestration, as indicated by the level of total and antibody-bound radiotracer partitioning to aqueous fecal extracts. Similarly, when a mixture of 125I-pHP-AAF and IgG were injected directly into the small intestine, more radioactivity appeared in the feces of mice given specific antibody. High-performance liquid chromatography analysis of aqueous fecal extracts indicated that the majority of fecal radiotracer from specific-antibody dosed mice was unmetabolized parent compound. Thus, peroral administration of AAF-specific antibodies mixed with 125I-pHP-AAF decreased gastrointestinal absorption and increased fecal excretion of the radiotracer, suggesting a novel mechanism for protection against environmental carcinogens.
Rasmussen
M V
MV
Department of Animal Science, University of Connecticut, CANR, Storrs 06269, USA.
Silbart
L K
LK
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D000918:Antibody Specificity; D001682:Biological Availability; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry*; D005260:Female; D005772:Gastrointestinal Transit; D007074:Immunoglobulin G / Q000276:immunology; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C
D002273:Carcinogens; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; C117530:iodo-N-2-(4-hydroxyphenylacetamido)fluorene; D015073:2-Acetylaminofluorene