In-vitro metabolism of fluorinated diakylnitrosamines.
To elucidate differences in metabolism caused by fluorination of NDEA and NDBA, these compounds and their fluorinated analogs (NDEA-F3, NDEA-F6, NDBA-F3, NDBA-F6 and NDBA-F1 4) were incubated with rat liver microsomal fractions. Aldehydes, nitrite and unchanged nitrosamines were determined. Additionally, the mutagenicity was investigated with a Salmonella/mammalian microsome assay. NDEA-F6 and NDBA-F1 4 were not appreciably metabolized and were not mutagenic. NDEA, NDEA-F3, NDBA, NDBA-F3 and NDBA-F6 were dealkylated and, to a lesser extent, denitrosated. Dealkylation at the fluorinated alkyl group was inhibited, especially in the case of NDEA-F3. Whereas NDEA, NDBA, NDBA-F3 and NDBA-F6 were clearly mutagenic, mutagenicity of NDEA-F3 was only marginal.
D000818:Animals; D001711:Biotransformation; D003640:Dealkylation; D005461:Fluorine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D009153:Mutagens; D009602:Nitrosamines; D005461:Fluorine