Modification of benzo[a]pyrene-induced transformation of C3H/10T12 cells by pregnenolone-16α-carbonitrile and dexamethasone

The compounds pregnenolone-16α-carbonitrile (3β-hydroxypregn-5-en-20-one-16α-carbonitrile (PCN)) and dexamethasone (9α-fluoro-16-methylprednisolone (DEX)), both known inducers of microsomal enzymes in vivo were tested for their effect on benzo[a]pyrene (B[a]P)-induced transformation of $\text{C3H/10T}\text{1}\text{2}$ cells. Our data indicate that even though PCN and DEX slightly increase aryl hydrocarbon hydroxylase (AHH) activity and metabolism of B[a]P, they have opposite effects on cellular transformation. While DEX inhibited transformation by as much as 65% when added 20 h prior to the carcinogen, PCN enhanced transformation by as much as 250% at equivalent doses. Possible mechanisms by which PCN and DEX could exert opposite effects in altering B[a]P-induced transformation of $\text{C3H/10T}\text{1}\text{2}$ cells are discussed.