4-acetylaminostilbene has been researched along with 4-dimethylaminostilbene* in 3 studies
3 other study(ies) available for 4-acetylaminostilbene and 4-dimethylaminostilbene
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The tentative identification of DNA-adducts generated by trans-4-dimethylaminostilbene and trans-4-acetylaminostilbene in rats.
Tritium-labeled trans-4-dimethylaminostilbene (DAS) and trans-4-acetylaminostilbene (AAS) were administered orally to female Wistar rats. RNA and DNA were isolated from livers after 24 h and 28 days. Hydrolysates were analyzed by gel filtration and HPLC. Total binding to nucleic acids and elution profiles of hydrolysates were very similar for both aminostilbene derivatives. The large polar fraction eluting early in Sephadex LH20 chromatograms accounting for 60-80% of total DNA-bound radioactivity could not be assigned to individual base adducts and most likely is not due to incomplete hydrolysis but rather to cross-links between bases or proteins and bases. Of the total radioactivity bound to nucleic acids 6-7% in RNA and 3-5% in DNA could be tentatively identified as four isomeric, cyclic guanine adducts (predominantly (S,S)- and (R,R)-guanine-N2,beta-N3,alpha-N-acetylaminobibenzyl) by cochromatography with synthetic reference compounds. The most abundant single adduct accounting for 20-30% of RNA-bound radioactivity (fraction G in Sephadex LH20 chromatography) could not be identified. The long-term experiment revealed different persistence of DNA adducts: the polar material decreased to about 2/3, the cyclic guanine adducts (fraction d-B) to about 1/3 to 1/2 within 4 weeks, whereas one of the unidentified DNA-adducts (fraction d-E) persisted completely. AAS labeled in the acetyl group was administered in an additional experiment. The presence of the acetyl group could be demonstrated in most of the adducts, but non-acetylated adducts were found also. The ratio of non-acetylated:acetylated cyclic B-adducts in RNA was 1:2 from DAS and 1:13 from AAS, in DNA 1:3 and 1:10, respectively. Topics: Animals; Carcinogens; Chemical Phenomena; Chemistry; Chromatography, Gel; Chromatography, High Pressure Liquid; DNA; Female; Liver; Rats; Rats, Inbred Strains; RNA; Stilbenes | 1990 |
Significance of metabolic activation and binding to nucleic acids of aminostilbene derivatives in vivo.
Comparison of metabolite binding of several aminostilbene-related compounds to rat liver macromolecules in vivo supported the concept that metabolic activation is a prerequisite for biologic activity. Carcinogenic trans-4-dimethylaminostilbene and trans-4-acetylaminostilbene bound more strongly to DNA than the biologically less active cis-4-acetylaminostilbene and 4-dimethylaminobibenzyl by more than ten times. Hydroxamic acid esters did not appear to be the major metabolites which ultimately reacted with nucleic acids. The primary biochemical lesions are not correlated with tissue susceptibility. Total binding of trans-4-dimethylaminostilbene metabolites to nucleic acids was highest in the liver, about one-fifth of that total amount in the kidney, less than one-fifth in the lung and glandular stomach (which is the target tissue for acute toxicity), and still less in the forestomach and Zymbal's gland, the tissue in which tumors arise after repeated administration of test compounds to female Wistar rats. In the nontarget tissues, i.e., liver and kidney, nucleic acid binding was not only initially high but also persistent. Therefore, the exposure-related, primary biochemical lesion could not be linked to the biologic lesion. Tissue-specific parameters, other than those related to metabolic activation, are proposed to determine the biologic effect. Topics: Animals; Bibenzyls; Biotransformation; Carcinogens; DNA; Kinetics; Liver; Proteins; Rats; RNA, Ribosomal; Stilbenes | 1981 |
Correlation of nucleic acid binding by metabolites of trans-4-aminostilbene derivatives with tissue specific acute toxicity and carcinogenicity in rats.
The reaction with macromolecules was determined in various tissues of female Wistar rats 24 h following a single oral administration of [3H]-trans-4-dimethylamino- and [3H]-trans-4-acetylaminostilbene. Total binding to proteins was 4-9 times greater than to nucleic acids in most tissues. Binding to RNA and DNA was very similar and greatest in liver, about 1/4 in kidney and 1/8 - 1/10 in lung, glandular stomach (target tissue for acute toxicity), bladder, mammary glands and Zymbal glands (target tissue for carcinogenicity). The target tissues, therefore, appear not to be notably exposed to reactive metabolites. The pattern of adducts was analyzed by Sephadex LH20 chromatography of RNA and DNA hydrolysates from liver, glandular stomach, lung and kidney. It was found to be very similar qualitatively. DNA-bound metabolites were very persistent in the non-target tissues liver and kidney, t 1/2 being 34 and 60 days, respectively. Some of the major adducts in liver were not eliminated at all within 4 weeks. It thus appears that aminostilbene derivatives represent examples of strong and genotoxic carcinogens for which the extent and persistence of primary DNA lesions are not correlated with the biological effect. Topics: Animals; Carcinogens; Chromatography, High Pressure Liquid; DNA; DNA Adducts; Female; Kidney; Liver; Organ Specificity; Protein Binding; Proteins; Rats; Rats, Wistar; RNA, Ribosomal; Stilbenes; Tritium | 1980 |