Disease relevance of NSC176336

• Prostate adenocarcinoma in rats: induction by 3,2'-dimethyl-4-aminobiphenyl [1].
• Prostatic carcinomas were found in 18 of 21 rats (85.7%) after this treatment but in only 1 of 19 rats (5.2%) maintained on normal diet throughout the experiment but given 3,2'-dimethyl-4-aminobiphenyl at the same times as the diet given to test rats [2].
• At 7 weeks of age, all animals, except vehicle-treated groups, received weekly s.c. injections of 50 mg 3,2'-dimethyl-4-aminobiphenyl (DMAB) per kg body weight for 20 weeks [3].
• Pancreatic acinar cell lesions, including foci, nodules, adenomas and in situ carcinomas, were found in male F344 rats given s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) at doses ranging from 50 to 167 mg/kg body weight in two 60-week experiments [4].
• This study was undertaken to investigate the possible antimutagenic effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced mutagenicity, using the Ames Salmonella/mammalian microsome system [5].

High impact information on NSC176336

• Acetylator genotype (NAT2)-dependent formation of aberrant crypts in congenic Syrian hamsters administered 3,2'-dimethyl-4-aminobiphenyl [6].
• Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate [7].
• The effects of varying dosages of 3,2'-dimethyl-4-aminobiphenyl (DMAB) in combination with cyclic dietary administration of ethinyl estradiol (EE) on induction of prostate carcinoma were investigated in male F344 rats [8].
• Male F344 rats were given a diet containing 0.75 ppm of ethinyl estradiol for 3 weeks and a basal diet for 2 weeks alternately 10 times, and 2 days after each change to basal diet (on the third day of feeding of the basal diet), a single s.c. injection of 50 mg/kg body weight of 3,2'-dimethyl-4-aminobiphenyl [2].
• A gene dose-response (NAT2*15/*15>NAT2*15/*16A>NAT2*16A/*16A) relationship was observed in liver and prostate cytosol towards the N-acetylation of p-aminobenzoic acid, 2-aminofluorene, beta-napthylamine, 4-aminobiphenyl, and 3,2'-dimethyl-4-aminobiphenyl [9].

Chemical compound and disease context of NSC176336

• In the present study we synthesized three caffeic acid esters, namely methyl caffeate (MC), phenylethyl caffeate (PEC) and phenylethyl dimethylcaffeate (PEDMC) and tested them against the 3,2'-dimethyl-4-aminobiphenyl, (DMAB, a colon and mammary carcinogen)-induced mutagenicity in Salmonella typhimurium strains TA 98 and TA 100 [10].

Biological context of NSC176336

• We investigated the mutagenic activation of 2-naphthylamine (2-NA), 3,2'-dimethyl-4-aminobiphenyl (DMAB), and 3,3'-dichlorobenzidine (DCB), bladder carcinogens, by renal and bladder microsomes and by purified P450s using the umu gene expression system, which detects DNA damage [11].
• Rat liver DNA damage by the non-hepatocarcinogen 3,2'-dimethyl-4-aminobiphenyl [12].
• In an attempt to induce a high incidence of prostate carcinoma, 3,2'-dimethyl-4-aminobiphenyl (DMAB), a prostatic carcinogen, was given during the period of cell proliferation of the prostate gland induced by the administration of methyltestosterone (MT) to castrated F344 rats [13].
• In order to investigate how and when metastases develop under experimental conditions, kinetics of the size and the number of lung metastasis lesions in F344 rats were examined after syngeneic transplantation of rat prostate carcinomas induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) [14].
• Glucuronides are often stable transport forms of carcinogens and in this way determine their organ specificity, for example in 2-naphthylamine-induced bladder carcinogenesis and in colon carcinogenesis produced by 2',3-dimethyl-4-aminobiphenyl [15].

Anatomical context of NSC176336

• Formation of DNA adducts in vivo in rat liver and intestinal epithelium after administration of the carcinogen 3,2'-dimethyl-4-aminobiphenyl and its hydroxamic acid [16].
• Ki-ras mutations with frequent normal allele loss versus absence of p53 mutations in rat prostate and seminal vesicle carcinomas induced with 3,2'-dimethyl-4-aminobiphenyl [17].
• Establishment and characterization of three androgen-independent, metastatic carcinoma cell lines from 3,2'-dimethyl-4-aminobiphenyl-induced prostatic tumors in F344 rats [18].
• 3,2'-Dimethyl-4-aminobiphenyl (DMAB), known to be a wide-spectrum genotoxic carcinogen in rats, is also tumorigenic to hamster organs such as the forestomach, small and large intestines, gallbladder and urinary bladder [19].
• F344 rats were repeatedly administered the prostate carcinogens 3,2'-dimethyl-4-aminobiphenyl (DMAB),N-nitrosobis(2-oxopropyl)amine(BOP), and N-methylnitrosourea (MNU) sequentially or together at times of hormonal castration induced regenerative cell proliferation of prostate epithelial cells [20].

Associations of NSC176336 with other chemical compounds

• Selective induction of rat urinary bladder tumors by simultaneous administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and butylated hydroxyanisole or butylated hydroxytoluene is associated with increased DMAB-DNA adduct formation [21].
• Human prostate tissue transplanted into nude mice was examined immunohistochemically for DNA adducts formed after administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) [22].
• Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation [23].
• Male F344 rats were given 10 biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks [24].
• Lack of tumorigenic response in the prostate gland of castrated F344 rats by 3,2'-dimethyl-4-aminobiphenyl given with methyltestosterone [13].

Gene context of NSC176336

• The colon carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMAB), like other arylamines, undergoes N-acetylation and O-acetylation by polymorphic acetyltransferase (NAT2) [25].
• A previous investigation demonstrated the anticarcinogenicity of acetaminophen (APAP) against colon carcinogenesis in rats induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) [26].

Analytical, diagnostic and therapeutic context of NSC176336

• Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats [27].
• Then, feeding was changed to basal diet and a single subcutaneous injection of 50 mg/kg body weight of 3,2'-dimethyl-4-aminobiphenyl (DMAB) was given two days after the change [28].
• Adjustment of milk fermented by L. delbrueckii ssp. bulgaricus 191R to pH 3, 7.6, or 13 prior to freeze-drying and acetone extraction did not significantly alter the activity specific for 3,2'-dimethyl-4-aminobiphenyl [29].
• We have previously shown that chronic administration of a pharmacological dose of testosterone propionate (TP) after treatment with the carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB), results in development of invasive and metastatic adenocarcinomas arising from the dorso-lateral and anterior prostate, as well as the seminal vesicles [30].

References