کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10847748 | 1070455 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Formation of the depurinating N3adenine and N7guanine adducts by reaction of DNA with hexestrol-3â²,4â²-quinone or enzyme-activated 3â²-hydroxyhexestrol
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
FAB-MSDMFESIdeoxyadenosineGUATFAADEMS/MS - MS / MSAdenine - آدنینDES - ازTrifluoroacetic acid - اسید TrifluoroaceticHES - او هستDiethylstilbestrol - دی اتیلستیل بسترولdimethylformamide - دی متیل فرمالیدDeoxyguanosine - دیوکسوگوئوزینfast atom bombardment mass spectrometry - طیف سنجی جرم اتم بوت شدن سریع اتمTandem mass spectrometry - طیف سنجی جرمی پشت سر هم یا متوالیHexestrol - هگزاسترولGuanine - گوانینelectrospray ionization - یونیزاسیون الکترو اسپری
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The nonsteroidal synthetic estrogen hexestrol (HES), which is diethylstilbestrol hydrogenated at the C-3-C-4 double bond, is carcinogenic. Its major metabolite is the catechol, 3â²-OH-HES, which can be metabolically converted to the catechol quinone, HES-3â²,4â²-Q. Study of HES was undertaken with the scope to substantiate evidence that natural catechol estrogen-3,4-quinones are endogenous carcinogenic metabolites. HES-3â²,4â²-Q was previously shown to react with deoxyguanosine to form the depurinating adduct 3â²-OH-HES-6â²-N7Gua by 1,4-Michael addition [Jan S-T, Devanesan PD, Stack DE, Ramanathan R, Byun J, Gross ML, et al. Metabolic activation and formation of DNAadducts of hexestrol,a synthetic nonsteroidal carcinogenic estrogen. Chem Res Toxicol 1998;11:412-9.]. We report here formation of the depurinating adduct 3â²-OH-HES-6â²-N3Ade by reaction of HES-3â²,4â²-Q with Ade by 1,4-Michael addition. The structure of the N3Ade adduct was established by NMR and MS. We also report here formation of the depurinating 3â²-OH-HES-6â²-N7Gua and 3â²-OH-HES-6â²-N3Ade adducts by reaction of HES-3â²,4â²-Q with DNA or by activation of 3â²-OH-HES by tyrosinase, lactoperoxidase, prostaglandin H synthase or 3-methylcholanthrene-induced rat liver microsomes in the presence of DNA. The N3Ade adduct was released instantaneously from DNA, whereas the N7Gua adduct was released with a half-life of approximately 3Â h. Much lower (<1%) levels of unidentified stable adducts were detected in the DNA from these reactions. These results are similar to those obtained by reaction of endogenous catechol estrogen-3,4-quinones with DNA. The similarities extend to the instantaneously-depurinating N3Ade adducts and relatively slowly-depurinating N7Gua adducts. The endogenous estrogens, estrone and estradiol, their 4-catechol estrogens and HES are carcinogenic in the kidney of Syrian golden hamsters. These results suggest that estrone (estradiol)-3,4-quinones and HES-3â²,4â²-Q are the ultimate carcinogenic metabolites of the natural and synthetic estrogens, respectively. Reaction of the electrophilic quinones by 1,4-Michael addition with DNA at the nucleophilic N-3 of Ade and N-7 of Gua is suggested to be the major critical step in tumor initiation by these compounds.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 70, Issue 1, January 2005, Pages 37-45
Journal: Steroids - Volume 70, Issue 1, January 2005, Pages 37-45
نویسندگان
Muhammad Saeed, Sandra J. Gunselman, Sheila Higginbotham, Eleanor Rogan, Ercole Cavalieri,