Comparison of the metabolism and DNA binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one by hamster embryo cells and the human hepatoma cell line HepG2.

Metabolism of 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one with hamster embryo cells and a human hepatoma cell line HepG2 is compared. Essentially, no metabolism was seen with hamster embryo cells but with the HepG2 cells, especially after induction with benzanthracene or Arochlor, this carcinogenic ketone was metabolized to give 1,2-dihydroxy-11-methyl-1,2,15, 16-tetrahydrocyclopenta[a]phenanthren-17-one, 3,4-dihydroxy-11-methyl-3,4,15,16-tetrahydrocyclopenta[a] phenanthren-17-one, 15,16-dihydro-15-hydroxy-11-methylcyclopenta[a]phenanthren-17-one, 15,16,-dihydro-16-hydroxy-11-methylcyclopenta[a]phenanthren-17- one, and three new metabolites, 16,17-dihydro-11-methyl-4,15,17-trihydroxy-15H-cyclopenta[a]phe phenanthrene, 15,16-dihydro-16,17-dihydroxy-11-methylcyclopenta[a]phenanthrene and 16,17-dihydro-11-methyl-15H-cyclopenta[a]phenanthren-17-ol. The reduction of the 17-ketone group and the formation of phenols with HepG2 cells appears to be the major difference between metabolism of 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one with HepG2 cells and rat liver microsomes. The metabolic products of this ketone also bind to DNA. These results suggest that the component of the aryl hydrocarbon hydroxylase enzyme system that is responsible for the activation of cyclopenta[a]phenanthrenes is specific and not the same as that needed for polycyclic aromatic hydrocarbons, and that HepG2 cells contain a reductase which is specific for the 17-ketone function in the cyclopenta[a]phenanthrenes.