Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is an analogue of quinoline, a hepatocarcinogen. 2-Aminofluorene, benzidine and 3,2'-dimethyl-4-aminobiphenyl (DMAB) are potent inducers of unscheduled DNA repair in primary culture rat liver hepatocytes, as was IQ (151 grains/nucleus at 1 X 10(-6) M). Quinoline, on the other hand, is only weakly positive in this assay (15 grains/nucleus at 1 X 10(-3) M). IQ, quinoline and DMAB were applied topically to shaved skin of Sencar mice with promotion by 12-O-tetradecanoylphorbol 13-acetate (TPA) for 20 weeks, when 14 of 20 mice in the quinoline group had 25 tumors, but only one of 30 animals in the IQ group and five of 30 in the DMAB group were tumor-bearing. Analogs of IQ synthesized by substitution at the 2- or 3-position with amino or methyl groups were assayed with the Ames Salmonella typhimurium tester strains TA98 and TA100. Mutagenicity for TA98 is reduced in the absence of the 3-methyl group and is completely abolished with removal of the 2-amino moiety. None of these analogs are strong mutagens for TA100. Exocyclic N-oxidation is a likely obligatory step in the activation of IQ to a mutagen.
Carcinogenesis 1985 Mar
PMID:Genotoxicity of the food mutagen 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) and analogs. 388 72

Dog is an animal model for assessing aromatic amine-induced bladder cancer, and hepatic N-glucuronidation is proposed as an important pathway leading to initiation of carcinogenesis. Therefore, benzidine N-glucuronidation was evaluated with dog liver microsomes and slices. Microsomal benzidine UDP-glucuronosyltransferase activity was increased with a variety of detergents. For kinetic analysis, native microsomal preparations were separated into treated (detergent treated, not centrifuged) or soluble (detergent treated, centrifuged) fractions. The detergents Triton X-100, Lubrol PX, Emulgen 911 and CHAPS increased the specific activity of treated fractions relative to the native microsomes 3- to 6-fold. The specific activities of the soluble fractions were highest with Emulgen 911 and CHAPS at a detergent-to-protein ratio of 1. Subsequent studies used Emulgen 911 or CHAPS. Similar results were observed with either preparation. For treated preparations, the Km and Vmax values were 0.142 +/- 0.006 mM and 0.65 +/- 0.1 nmol/mg protein/min respectively. A variety of chemicals were tested for their effect on benzidine N-glucuronide formation. At 0.1 mM, the only effective inhibitors (< 50% of control) were 2-aminofluorene, estriol, 17-epiestriol, 2-OH-estrone, and 4-OH-estrone. With Emulgen-treated microsomes, the Ki values for 2-aminofluorene, 4-aminobiphenyl and estriol were 0.114 +/- 0.014, 0.347 +/- 0.032 and 0.047 +/- 0.003 mM respectively. 2-Aminofluorene and estriol were non-competitive inhibitors, while 4-aminobiphenyl was a competitive inhibitor. Slices incubated with these chemicals exhibited an inhibition profile similar to that observed with microsomes. Thus, N-glucuronidation of benzidine may be an important metabolic pathway in dog. Inhibition of benzidine N-glucuronidation by estriol and catechol estrones may be important in vivo events in aromatic amine-induced carcinogenesis.
Carcinogenesis 1993 May
PMID:Benzidine glucuronidation in dog liver. 838 54

It is well documented that arylamine carcinogens are N-acetylated by cytosolic N-acetyltransferase (NAT) enzyme. NAT plays an important role in the metabolizing of those arylamine compounds. 2-Aminofluorene (AF) is an arylamine carcinogen which has been demonstrated to induce carcinogenesis in laboratory animals. Our previous study has shown that a human promyelocytic leukemia cell line, HL-60, displays NAT activity. The purpose of the present study was to determine whether or not wogonin could affect the N-acetylation of AF in HL-60. N-acetylated and non-N-acetylated AF were determined by using high performance liquid chromatography. Wogonin displayed a dose-dependent inhibition of NAT activity in cytosols and intact cells. Wogonin also decreased AF-DNA adduct formation in these cells. The effects of wogonin on the NAT enzymes levels were also examined by Western blotting and flow cytometry and the changes of NAT gene expression were examined by polymerase chain reaction (PCR) and cDNA microarray. The results demonstrated that wogonin inhibited NAT1 mRNA gene expression and the level of NAT enzyme in HL-60 cells. This is the first demonstration that wogonin affects human leukemia cells' NAT activity in vitro.
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PMID:Wogonin inhibits N-acetyltransferase activity and gene expression in human leukemia HL-60 cells. 1581 29