The 4-5S carcinogen binding protein binds 1-aminopyrene, 1-nitropyrene and (+)-benzo[a]pyrenediolepoxide and is found...

Twelve tissues from the BDA/2J mouse were examined in order to assess the tissue distribution of a soluble 4-5S carcinogen binding protein (CBP). The CBP binds numerous polycyclic aromatic hydrocarbons, regulates the expression of cytochrome P-450c and is a carrier protein of carcinogen metabolites. The highest specific binding was found in hepatic tissue (600 fmol per mg protein). The amount of CBP in the kidney and testis was about 60% of the value observed for the liver. Lower levels of CBP were observed in the reproductive tract (uterus and vagina), spleen, stomach, heart, urinary bladder, skin, large and small intestine and lung. It was shown that the CBP bound the environmental carcinogen 1-nitropyrene, its reduced metabolite 1-aminopyrene and the ultimate carcinogenic metabolite of benzo[a]pyrene or (+)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene but not the smaller coplanar PCB molecule, 3,3',4,4'-tetrachlorobiphenyl. The results suggest that (a) the CBP is not a tissue-specific protein in the mouse, (b) the ligands for the CBP are not limited to the unmetabolized procarcinogens but include both positively and negatively charged ligands, and (c) in vitro the CBP covalently binds the ultimate carcinogenic metabolite of benzo[a]pyrene.