title: Identification of an N-acetylcysteine conjugate in the urine after oral administration of 2,4-dichloro-1-nitrobenzene to rats.
abstract: Oral administration of 2,4-dichloro-1-nitrobenzene (2,4-DCNB) causes kidney tumors in the rat. The objective of the present study was to identify the chemical structure of 2,4-DCNB metabolites in urine. Urine from 2,4-DCNB fed rats was more yellow than urine from control rats, exhibiting a broad UV-spectrum around a peak wavelength of 360 nm; the control urine did not have an absorbance. The yellow component was extracted and analyzed. The optical properties of the yellow component were the same as the N-acetylcysteine conjugate of 1,4-dichloro-2-nitrobenzene (1,4-DCNB): 1,4-DCNB is secreted in urine as an N-acetylcysteine conjugate. LC-MS/MS analyses of this yellow component demonstrated its chemical structure to be the N-acetylcysteine conjugate of 2,4-DCNB. Nuclear overhauser effect and LC-MS/MS analyses revealed the structural isomer of this 2,4-DCNB metabolite as N-acetyl-S-(5-chloro-2-nitrophenyl)-L-cysteine. We also discuss the possibility that the N-acetylcysteine conjugate identified in this study plays a role as a proximate carcinogen in the formation of kidney tumors.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohnishi
authors.forename: Makoto
authors.initials: M
authors.lastname: Take
authors.forename: Seigo
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yajima