title: Mutagenic outcome of the urinary carcinogen 4-aminobiphenyl is increased in acidic pH.
abstract: One of the carcinogens from cigarette smoke, 4-aminobiphenyl, is excreted in urine as 4-N-hydroxyl aminobiphenyl metabolite conjugates that undergo pH mediated activation to nitreneum ions leading to bladder tumorigenesis via DNA adduct formation. We hypothesize that changing the pH of smokers' urine might impact the mutagenic outcome. 4-NOHABP was synthesized (∼98% purity), structure confirmed by TLC and NMR; mutagenic activity, assessed by the Ames test, was measured after pre-incubation in buffer solutions or human urine at pH 4, 6, 7 and 8. An inverse correlation was observed between number of histidine revertant colonies and pH (r(2)=0.89), 4-NOHABP exhibiting significant mutagenicity at pH 4.0 (P<0.05).
authors.affiliation: School of Pharmacy at MCV Campus, Virginia Commonwealth University, Smith Building, Room 356C, Richmond, VA 23298-0533, USA.
authors.forename: Mohamadi A
authors.initials: MA
authors.lastname: Sarkar
authors.forename: Unyime O
authors.initials: UO
authors.lastname: Nseyo
authors.forename: Bao-Zhen
authors.initials: BZ
authors.lastname: Zhong