Renal protein biomarkers of lead exposure.
Kanitz-MH; Zhu-H; Snawder-JE; Moorman-WJ; Skaggs-SR; Fultz-CD; Witzmann-FA; Savage-RE
Toxicologist 1998 Mar; 42(1-S):378
To develop a set of protein markers of renal lead exposure and effect, we investigated renal protein expression while approximating occupational lead exposure at subchronic, low blood levels. Lead was administered to male Dutch Belted rabbits as a lead acetate solution adjusted weekly to achieve and maintain the target blood lead levels of O, 20, 40, and 80 ug/dL for 15 weeks. Rabbits were sacrificed and kidneys removed and frozen. The homogenates were solubilized for large-scale two-dimensional electrophoresis (2-DE). Proteins were separated by conventional ISO-DALT 2-DE, gels were stained. and the resulting protein patterns image-analyzed. Minor proteins were quantitatively altered (P<.05) by lead exposure (12 proteins by 20 ug/dL exposure, 25 by 40ug/dL and 102 by 80 ug/dL). The more liberal confidence interval may be associated with a high probability of Type 1 error. Using the more reliable interval P<.001 401ug/L blood lead resulted in only one protein alteration and 80 ug/dL affected 14 proteins. Although the identity of all effected proteins remains unknown, we have tentatively identified a set of quantitatively altered charge variants as isoforms of glutathione S- transferase (GST) based on similar observations in rodents subjected to short-term, very high lead exposures. The significance of the protein alterations as markers of toxicity and toxic mechanism awaits their conclusive identification. These experiments are currently underway.
Lead-absorption; Lead-poisoning; Renal-absorption; Renal-toxicity; Proteins; Animal-studies; Animals; Laboratory-animals; Laboratory-testing; Toxins; Kidney-disorders; Biomarkers
The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington