Metabolism and DNA binding of polycyclic aromatic hydrocarbons by human diploid fibroblasts

✍ Scribed by William M. Baird; Leila Diamond

• Publisher: John Wiley and Sons
• Year: 1978
• Tongue: French
• Weight: 639 KB
• Volume: 22
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910220213

✦ Synopsis

Abstract

The metabolism of three carcinogenic polycyclic aromatic hydrocarbons was measured in mid‐(population doubling levels of 20–39) and late‐(population doubling levels > 55) passage cultures of WI‐38 human diploid fibroblasts. Cultures of mid‐and late‐passage cells metabolized these hydrocarbons to both water‐ and organic solvent‐soluble derivatives. In stationary cultures, the same amounts of benzo(a)pyrene (BP) and 3‐methyl‐cholanthrene were metabolized per cell, but late‐passage cells metabolized only one‐third as much 7,12‐dimethylbenz(a)anthracene per cell as mid‐passage cells. The DNA adducts formed from BP in WI‐38 cells were examined by chromatography of enzyme‐degraded DNA samples on Sephadex LH20 columns. On columns eluted with methanol‐water gradients, the [^3^H]BP‐deoxyribonucleoside adducts eluted in the same volume as the product peak isolated from DNA that had been reacted with 7,8‐dihydroxy‐9,10‐epoxy‐7,8,9,10‐tetrahydroBP. On columns eluted with borate‐containing methanol‐water gradients, 62% of the cellular products eluted in the same volume as the product peak isolated from DNA that had been reacted with (±) 7α,8β‐dihydroxy‐9β,10β‐epoxy‐7,8,9,10‐tetrahydroBP (the anti‐isomer) and 35% eluted in the same volume as a product peak isolated from DNA that had been reacted with (±) 7α,8β‐dihydroxy‐9α,10α‐epoxy‐7,8,9,10‐tetrahydroBP (the syn‐isomer). Thus, more than one type of DNA adduct is formed in these cells, possibly through the reacticn of different isomers of this BP‐diol‐epoxide with DNA.