The rat hepatoma cell line McA RH7777 was cloned into alpha-fetoprotein-producing (AFP(+)) and non-producing (AFP(-)) sublines, A monoclonal antibody (MAb A2/3) reacting with an antigen (Ag A2/3) present only in AFP(-) clones or AFP(-) cells in mixed clones was obtained, Ag A2/3 was absent from the liver of embryonic, fetal, newborn and adult rats, but it was present in gastric and intestinal mucosa of adult rats, Ag A2/3 was found to be a heavy metal-inducible protein: Cd2+ and Pb2+ strongly induced the expression of Ag A2/3 in vivo in the liver of adult rats, while xenobiotics and CCl4 were not active in this respect. In vitro Cd2+ and Pb2+ induced Ag A2/3 expression in several AFP(+) clones, leading to a simultaneous marked decrease of AFP(+) cells from such clones, The effect of Cd2+ in the induction of Ag A2/3 and suppression of AFP was reversible, SDS PACE revealed one protein band with an m.w. close to 45,000, which was not sensitive to mercaptoethanol. Despite its inducible properties, Ag A2/3 was shown not to belong to metallothioneins, cytochrome P-450, glutathion-transferase or heat shock proteins families, well-known as being inducible cell stress proteins. Expression of Ag A2/3 could be one of the factors determining the high amplitude of AFP production by individual liver tumors. The nature of Ag A2/3 and its alternative expression with respect to AFP remain to be studied. (C) 1998 Wiley-Liss, Inc.