ANTICARCINOGENIC ACTIVITY OF INDOLE-3-CARBINOL ACID PRODUCTS - ULTRASENSITIVE BIOASSAY BY TROUT EMBRYO MICROINJECTION

The relative contribution of indole-3-carbinol (I3C) and its acid cond ensation products to the anticarcinogenic activity of this crucifer ph ytochemical has been studied using trout embryo microinjection. I3C wa s treated with 0.07 N HCl to give a reaction mixture (RXM) comprising <0.5 %, parent compound and over 20 products, the most prevalent being the dimer 3,3'-diindolylmethane (I33') and a related cyclic trimer (C T). RXM, 133' or CT was injected into embryos with [H-3]anatoxin B-1 ( AFB(1)) and total embryonic DNA was isolated 1, 3, or 10 days postinje ction. Compared with controls given AFB(1) alone, I3C failed to inhibi t carcinogen-DNA binding at any time point In contrast 133', CT, and R XM inhibited AFB(1)-DNA binding by an average of 37, 51, and 65%, resp ectively. Coinjection of AFB(1) and 350 mu M I3C, RXM, or I33' into tr out embryos reduced AFB(1)-induced hepatocarcinogenesis after 1 year f rom 43.4% in positive controls to 36.0, 12.2 (P < 0.05), and 24.6% (P < 0.05), respectively. No tumor data were obtained in the AFB, plus CT group due to poor survival of the embryos posthatching, These results indicate that acid condensation products, not the parent compound, re present the anticarcinogenic species in trout and that their formation in the stomach is a likely prerequisite for I3C anticarcinogenesis.