PERORAL ADMINISTRATION OF SPECIFIC ANTIBODY ENHANCES CARCINOGEN EXCRETION

Ingested carcinogens may exert effects directly on the gastrointestina l epithelium or after absorption and transport to other tissues. To de termine the effect of anti-carcinogen antibody ingestion on dietary ca rcinogen excretion, a mixture of specific IEA or IgG and the model car cinogen I-125-N-2-(4-hydroxyphenyl-acetamido) fluorene (I-125-pHP-AAF) was perorally administered to mice. These mice excreted more total an d antibody-bound radiotracer in feces compared with controls given a s imilar mixture containing nonspecific antibody. In addition, urinary r adiotracer excretion was reduced by 96% in specific-antibody dosed mic e, indicating reduced gastrointestinal absorption of I-125-pHP-AAF. Re duced 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 I-125-PH-AAF. Specific antibody treatment consistently increased intraluminal radio tracer sequestration, as indicated by the level of total and antibody- bound radiotracer partitioning to aqueous fecal extracts. Similarly, w hen a mixture of I-125-pHP-AAF and IgG were injected directly into the small intestine, more radioactivity appeared in the feces of mice giv en specific antibody. High-performance liquid chromatography analysis of aqueous fecal extracts indicated that the majority of fecal radiotr acer from specific-antibody dosed mice was unmetabolized parent compou nd. Thus, peroral administration of AAF-specific antibodies mixed with I-125-pHP-AAF decreased gastrointestinal absorption and increased fec al excretion of the radiotracer, suggesting a novel mechanism for prot ection against environmental carcinogens.