کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597538 1562410 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oxidation of alcohols and reduction of aldehydes derived from methyl- and dimethylpyrenes by cDNA-expressed human alcohol dehydrogenases
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Oxidation of alcohols and reduction of aldehydes derived from methyl- and dimethylpyrenes by cDNA-expressed human alcohol dehydrogenases
چکیده انگلیسی

Some methylated pyrenes can form DNA adducts in rat tissues after benzylic hydroxylation and sulpho conjugation. However, oxidation of the intermediate alcohols to carboxylic acids is an important competing pathway leading to detoxification. We previously showed that co-administration of ethanol or 4-methylpyrazole strongly enhances DNA adduct formation by 1-hydroxymethylpyrene, indicating an involvement of alcohol dehydrogenases (ADHs) in the detoxification. This mechanism may be involved in the observed synergism of smoking and alcohol consumption in certain human cancers. In a preceding study, cDNA-expressed human ADH2 efficiently oxidised 1-, 2- and 4-hydroxymethylpyrene; these reactions were inhibited in the presence of ethanol or 4-methylpyrazole. Here we report that ADH1C, ADH3 and ADH4 also show substantial activity towards these substrates and two further congeners, 1-hydroxymethyl-6-methylpyrene and 1-hydroxymethyl-8-methylpyrene. All four ADH forms also catalysed the reverse reaction, implying that the aldehydes have to be sequestered by other enzymes, such as aldehyde dehydrogenases, for final detoxification. ADH1C and ADH4 activities towards hydroxymethylpyrenes were more strongly inhibited in the presence of ethanol and 4-methylpyrazole than those of ADH2. ADH3 was only inhibited at very high concentrations of the modulators. In conclusions, several human ADHs are capable of detoxifying benzylic alcohols of alkylated polycyclic aromatic hydrocarbons. However, some competing substrates and inhibitors may affect all these redundant detoxification systems, although to various extents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 245, Issues 1–2, 12 March 2008, Pages 65–75
نویسندگان
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