Disease relevance of CCRIS 26

• The bile samples from rats inoculated with 4-aminobiphenyl were mutagenic for Salmonella typhimurium TA100 only in the presence of beta-glucuronidase, whereas those from the 3,2'-dimethyl-4-aminobiphenyl-treated rats did not require the enzyme for mutagenicity toward strain TA100 [1].
• Measurement of 4-aminobiphenyl-hemoglobin adducts in lung cancer cases and controls [2].
• Mutagenesis by N-acetoxy-N-trifluoroacetyl-4-aminobiphenyl, a reactive form of the human bladder carcinogen 4-aminobiphenyl (ABP), was studied in Escherichia coli virus M13mp10 [3].
• Other biological processes, such as toxicity and regenerative proliferation, can significantly influence the dose response of 4-aminobiphenyl-induced tumors [4].
• The global genomic repair of DNA adducts was examined in human papillary transitional cell carcinoma (TCC) cell lines after exposure to N:-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), the proximate carcinogenic metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP) [5].

High impact information on CCRIS 26

• METHODS: One hundred thirty-three male residents of Los Angeles County who were either white, black, or Asian (Chinese or Japanese) and over the age of 35 years were assessed for their acetylator phenotype and levels of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts [6].
• 4-Aminobiphenyl hemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero [7].
• Maternal-fetal exchange of a potent tobacco-related human carcinogen, 4-aminobiphenyl, was studied in smoking (n = 14) and nonsmoking (n = 38) pregnant women [7].
• A measure of third-trimester tobacco smoke exposure based on number of cigarettes smoked per day, amount of each cigarette smoked, and depth of inhalation was associated (r2 = .59, P = .029) with maternal 4-aminobiphenyl levels but not with fetal 4-aminobiphenyl levels [7].
• Administration of a dietary supplement of 6 g D,L tryptophan/day for 4 1/2 years following the administration of a single dose of 50 mg 4-aminobiphenyl/kg produced a bladder tumor in 1 of 4 beagle dogs [8].

Chemical compound and disease context of CCRIS 26

• Hemoglobin adducts of the activated carcinogenic aromatic amine 4-aminobiphenyl have been measured in a case-control study of lung cancer [2].
• The duplex genome of Escherichia coli virus M13mp10 was modified at a unique site to contain N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG8-ABP), the major carcinogen-DNA adduct of the human bladder carcinogen 4-aminobiphenyl [9].
• Benzidine and 4-aminobiphenyl (4-ABP) are activated by intact plant cells and cell free TX1MX into mutagenic metabolites that induce frameshift and base pair substitution mutations in Salmonella typhimurium [10].
• Alkyl and trifluoromethyl derivatives of 4-aminobiphenyl (1) (4ABP) and 2-aminofluorene (7) (2AF) were synthesised and assayed for mutagenicity using Salmonella typhimurium tester strains TA98 and TA100 with and without the addition of S9 mix [11].
• Human and Escherichia coli beta-glucuronidase hydrolysis of glucuronide conjugates of benzidine and 4-aminobiphenyl, and their hydroxy metabolites [12].

Biological context of CCRIS 26

• Adduct detection by acylation with [35S]methionine: analysis of DNA adducts of 4-aminobiphenyl [13].
• 32P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene [14].
• Frequency of urination and its effects on metabolism, pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in beagle dogs given the carcinogen 4-aminobiphenyl [15].
• The demonstration that both the genetically determined slow acetylator phenotype and tobacco smoking are independently associated with levels of the carcinogen 4-aminobiphenyl in adducted hemoglobin suggests a single mechanism to explain the contribution of genetic susceptibility and environmental exposure in bladder carcinogenesis [16].
• A sensitive 32P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation [14].

Anatomical context of CCRIS 26

• Bladder transitional epithelial microsomes also activated o-dianisidine, 4-aminobiphenyl, and 2-naphthylamine to bind to protein and transfer RNA and benzidine and O-dianisidine to bind DNA [17].
• Congenic Bio. 82.73/H Syrian hamsters expressed acetylator genotype-dependent N-acetyltransferase activity in colon cytosols toward arylamine carcinogens such as 2-aminofluorene and 4-aminobiphenyl [18].
• Addition of the plant phenolic flavonoid (+)-catechin to rat liver microsomes inhibited the mutagenicity of the aromatic amines 2-aminofluorene and 4-aminobiphenyl in the Ames test [19].
• Bovine bladder mucosa microsomal cytochrome P-450 and 4-aminobiphenyl N-hydroxylase activity [20].
• The monitored biomarkers included: DNA adducts in bronchoalveolar lavage cells, tracheal epithelium, lung and heart; oxidative damage to pulmonary DNA; hemoglobin adducts of 4-aminobiphenyl and benzo(a)pyrene-7,8-diol-9,10-epoxide; micronucleated and polynucleated alveolar macrophages and micronucleated polychromatic erythrocytes in bone marrow [21].

Associations of CCRIS 26 with other chemical compounds

• Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4'-methylene-bis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases [22].
• Specificity of mutagenesis by 4-aminobiphenyl. A possible role for N-(deoxyadenosin-8-yl)-4-aminobiphenyl as a premutational lesion [3].
• 4-Aminobiphenyl and DNA Reactivity: Case Study Within the Context of the 2006 IPCS Human Relevance Framework for Analysis of a Cancer Mode of Action for Humans [4].
• This study reveals why human NAT1 acetylates the sunscreen additive p-aminobenzoic acid and tobacco smoke carcinogen 4-aminobiphenyl, but not o-toluidine and other arylamines linked to bladder cancer [23].
• The study presented here describes the analysis of DNA adducts in the human TK6 lymphoblastoid cell line after exposure to N-hydroxy-4-aminobiphenyl, a mutagenic metabolite of 4-aminobiphenyl [24].

Gene context of CCRIS 26

• Beginning in January 1992, all case patients and their matched control subjects were asked for a blood sample donation at the end of the in-person interviews for measurements of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts, and glutathione S-transferases M1/T1/P1 (GSTM1/T1/P1) and N-acetyltransferase-1 (NAT1) genotypes [25].
• UGT1A9 metabolized 4-aminobiphenyl approximately 50% faster than benzidine or N-acetylbenzidine [26].
• N-acetyltransferase activity toward the aromatic amine carcinogen 4-aminobiphenyl and O-acetyltransferase activity toward its proximate metabolite N-hydroxy-4-aminobiphenyl were both present in tissue cytosols of WT mice but were undetectable in Nat2 KO mice [27].
• CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice [28].
• UGT1A5 did not glucuronidate 4-aminobiphenyl, a good substrate for the highly homologous enzymes UGT1A4 and UGT1A3 [29].

Analytical, diagnostic and therapeutic context of CCRIS 26

• Mice treated with 4-aminobiphenyl showed some depression of interferon production 2 hr after treatment, maximum inhibition of interferon induction 24 hr after treatment, and a return to control levels of interferon 48 hr after treatment [30].
• Detection and characterization of carcinogen-DNA adducts in exfoliated urothelial cells from 4-aminobiphenyl-treated dogs by 32P-postlabelling and subsequent thin-layer and high-pressure liquid chromatography [31].
• Characterization by fast atom bombardment mass spectrometry confirmed the structure as an intact 4-aminobiphenyl-modified tetranucleotide, while 1H nuclear magnetic resonance spectroscopy established the site of substitution and the existence of ring stacking between the carcinogen residue and DNA bases [9].
• We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 2,400 4-aminobiphenyl (4-AB) +S9-induced revertants of the -1 frameshift allele hisD3052 and of the base-substitution allele hisG46 of Salmonella typhimurium [32].
• After 2 hr of incubation, the N-glucuronide of 4-aminobiphenyl represented 52 and 27% of the total radioactivity recovered by HPLC in dog and human, respectively [33].

References