Comparative metabolism of 7,12-dimethylbenz[a]-anthracene and its non-carcinogenic 2-fluoro analogue by Syrian hamster embryo cells.
The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) and its non-carcinogenic 2-fluoro analogue (2F-DMBA) by Syrian hamster embyro (SHE) cells has been studied using high pressure liquid chromatography (HPLC) and fluorescence spectroscopy. Metabolites produced by SHE cells were compared chromatographically to those produced on a larger scale by liver microsomal preparations and previously identified by gas chromatography and mass spectrometry. At least 2 (possibly 3) phenol metabolites, none of which appear to be in the A-ring, were formed from [3H] 2F-DMBA and totalled only 3% of the organic extractable activity present in the media at 24 h. On the other hand, 3 A-ring phenols (DMBA-2-ol, DMBA-3-ol and DMBA-4-ol) comprising almost 12% of the total organic extractable radioactivity at 24 h were identified as metabolites in SHE cell culture media. For both hydrocarbons the major organic extractable metabolite present at 24 h was the respective 8,9-dihydro-dihydroxydiol (DMBA 45%, 2F-DMBA 39%). Thus, substitution of fluorine for hydrogen at the 2-carbon of DMBA appears to block or greatly reduce the A-ring metabolism of this compound but has relatively little effect on D-ring oxidation. Therefore loss of the carcinogenic/mutagenic activity of DMBA correlates with the extent of A-ring metabolism including, possibly, the bay region diol epoxide.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004622:Embryo, Mammalian; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013050:Spectrometry, Fluorescence
D001551:Benz(a)Anthracenes; D006845:Hydrocarbons, Fluorinated; D015127:9,10-Dimethyl-1,2-benzanthracene