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 ca...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1986-01, Vol.7 (1), p.143-148
Main Author: BHATT, T. S
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - metabolism
Carcinoma, Hepatocellular - metabolism
Cell Line
Chemical agents
Chromatography, High Pressure Liquid
Cricetinae
DNA - metabolism
DNA, Neoplasm - metabolism
Embryo, Mammalian
Gonanes - metabolism
Humans
Liver Neoplasms - metabolism
Medical sciences
Microsomes - metabolism
Tumors
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Summary: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-tetrahy-drocyclopenta[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]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.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/7.1.143