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ToxSci Advance Access published online on May 21, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm126
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© The Author 2007. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Globin S-Propyl Cysteine and Urinary N-Acetyl-S-Propyl Cysteine as Internal Biomarkers of 1-Bromopropane Exposure

Holly Valentine*, Kalyani Amarnath*, Venkataraman Amarnath*, Weihua Li{dagger}, Xuncheng Ding{dagger}, William M. Valentine* and Gaku Ichihara§

* Department of Pathology, Vanderbilt University Medical Center, 1161 21st Ave S., Nashville, Tennessee, 37232-2561 {dagger} Shanghai Institute of Planned Parenthood Research, WHO Collaborating Center for Research Reproduction, Shanghai, 200032, China § Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan

Correspondence to: Holly L. Valentine, Fax: (615) 343-9825. E-mail: holly.valentine{at}vanderbilt.edu

Received May 4, 2007; revision received May 4, 2007; accepted May 8, 2007


  Abstract

1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is a neuro and reproductive toxicant in animals and humans. In this study, the dose responses for urinary AcPrCys and S-propylcysteine (PrCys) adducts on globin and neurofilaments were determined as a function of 1-BP exposure level and duration in the rat; and globin PrCys adducts and urinary AcPrCys were quantified in samples obtained from workers in a 1-BP production facility. Rats were exposed to 1-BP by inhalation for two weeks at 0, 50, 200, or 800 ppm and to 1-BP at 0 or 50 ppm for 4 weeks. After the 4 week exposures ended, half of the animals were euthanized immediately and half euthanized 8 days later. Urinary AcPrCys was measured using LC/MS/MS and GC/MS; and PrCys adducts were determined on globin and neurofilaments using LC/MS/MS. In rats, PrCys adduct and urinary AcPrCys levels demonstrated a linear dose response relative to exposure level. PrCys globin adducts demonstrated a linear cumulative dose response over the 4-week exposure period. Elimination of AcPrCys appeared biphasic with detectable levels still present in urine up to 8 days post-exposure. A significant increase in globin PrCys adducts was observed in the 1-BP workers relative to control workers; and urinary AcPrCys increased with increasing 1-BP ambient exposure levels. The results of these studies demonstrate the ability of 1-BP to covalently modify proteins in vivo and support the potential of urinary AcPrCys and globin PrCys adducts to serve as biomarkers of 1-BP exposure in humans.

Key Words: 1-bromopropane; protein adduct; globin; neurofilaments; mercapturate; biomarkers.


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[Abstract] [Full Text] [PDF]


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