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: Makoto Ohnishi, Makoto Take, Seigo Yamamoto, Shoji Fukushima, Hirofumi Yajima
• Journal: The Journal of toxicological sciences (J Toxicol Sci) Vol. 34 Issue 2 Pg. 233-7 (Apr 2009) ISSN: 1880-3989 [Electronic] Japan
• PMID: 19336981 (Publication Type: Letter)

Chemical References

• Carcinogens
• Nitrobenzenes
• 2,4-dichloro-1-nitrobenzene
• Acetylcysteine

Topics

• Acetylcysteine (analysis, urine)
• Administration, Oral
• Animals
• Carcinogens (pharmacokinetics)
• Magnetic Resonance Spectroscopy
• Male
• Nitrobenzenes (pharmacokinetics)
• Rats
• Rats, Inbred F344
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Ultraviolet
• Tandem Mass Spectrometry