Abstract
Hexachlorobutadiene (HCBD), a renal toxin and carcinogen is thought to require bioactivation to exert toxicity. The chemically synthesized cysteine conjugate of structurally similar halogenated hydrocarbons, trichloroethylene, chlorotrifluoroethylene, and chlorodifluoroethylene, have been shown to be nephrotoxic. Hence the cysteine conjugate of HCBD, S-pentachlorobuta-1,3-dienyl cysteine (PCBC), was assessed for potential nephrotoxicity. Active acid and base transport in isolated rabbit renal tubules was used to screen nephrotoxicity. A dose-dependent decrease in acid and base transport was observed after incubation with PCBC. At 10-5 M PCBC transport was similar to that in controls, while at 10-3 M PCBC completely inhibited active transport. In addition, in vivo exposure of Swiss-Webster male mice caused dose-dependent damage in the pars recta region of the proximal tubules (5-25 mg/kg ip). Genotoxicity in renal tissue was studied by using alkaline elution to detect DNA single-strand breaks and total cross-links. No DNA single-strand breaks were observed in isolated rabbit renal tubules after exposure to 10-3 to 10-5 M PCBC. However, at 10-3 M PCBC there was some evidence of DNA cross-links. Therefore if cysteine conjugates of HCBD are formed in vivo, they could account for the toxicity observed with exposure to HCBD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 857-867 |
| Number of pages | 11 |
| Journal | Journal of Toxicology and Environmental Health |
| Volume | 11 |
| Issue number | 4-6 |
| State | Published - 1983 |
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ASJC Scopus subject areas
- Pollution
- Toxicology
Cite this
In vivo and in vitro nephrotoxicity of the cysteine conjugate of hexachlorobutadiene. / Jaffe, D. R.; Hassall, C. D.; Brendel, K.; Gandolfi, A Jay.
In: Journal of Toxicology and Environmental Health, Vol. 11, No. 4-6, 1983, p. 857-867.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo and in vitro nephrotoxicity of the cysteine conjugate of hexachlorobutadiene
AU - Jaffe, D. R.
AU - Hassall, C. D.
AU - Brendel, K.
AU - Gandolfi, A Jay
PY - 1983
Y1 - 1983
N2 - Hexachlorobutadiene (HCBD), a renal toxin and carcinogen is thought to require bioactivation to exert toxicity. The chemically synthesized cysteine conjugate of structurally similar halogenated hydrocarbons, trichloroethylene, chlorotrifluoroethylene, and chlorodifluoroethylene, have been shown to be nephrotoxic. Hence the cysteine conjugate of HCBD, S-pentachlorobuta-1,3-dienyl cysteine (PCBC), was assessed for potential nephrotoxicity. Active acid and base transport in isolated rabbit renal tubules was used to screen nephrotoxicity. A dose-dependent decrease in acid and base transport was observed after incubation with PCBC. At 10-5 M PCBC transport was similar to that in controls, while at 10-3 M PCBC completely inhibited active transport. In addition, in vivo exposure of Swiss-Webster male mice caused dose-dependent damage in the pars recta region of the proximal tubules (5-25 mg/kg ip). Genotoxicity in renal tissue was studied by using alkaline elution to detect DNA single-strand breaks and total cross-links. No DNA single-strand breaks were observed in isolated rabbit renal tubules after exposure to 10-3 to 10-5 M PCBC. However, at 10-3 M PCBC there was some evidence of DNA cross-links. Therefore if cysteine conjugates of HCBD are formed in vivo, they could account for the toxicity observed with exposure to HCBD.
AB - Hexachlorobutadiene (HCBD), a renal toxin and carcinogen is thought to require bioactivation to exert toxicity. The chemically synthesized cysteine conjugate of structurally similar halogenated hydrocarbons, trichloroethylene, chlorotrifluoroethylene, and chlorodifluoroethylene, have been shown to be nephrotoxic. Hence the cysteine conjugate of HCBD, S-pentachlorobuta-1,3-dienyl cysteine (PCBC), was assessed for potential nephrotoxicity. Active acid and base transport in isolated rabbit renal tubules was used to screen nephrotoxicity. A dose-dependent decrease in acid and base transport was observed after incubation with PCBC. At 10-5 M PCBC transport was similar to that in controls, while at 10-3 M PCBC completely inhibited active transport. In addition, in vivo exposure of Swiss-Webster male mice caused dose-dependent damage in the pars recta region of the proximal tubules (5-25 mg/kg ip). Genotoxicity in renal tissue was studied by using alkaline elution to detect DNA single-strand breaks and total cross-links. No DNA single-strand breaks were observed in isolated rabbit renal tubules after exposure to 10-3 to 10-5 M PCBC. However, at 10-3 M PCBC there was some evidence of DNA cross-links. Therefore if cysteine conjugates of HCBD are formed in vivo, they could account for the toxicity observed with exposure to HCBD.
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UR - http://www.scopus.com/inward/citedby.url?scp=0020609675&partnerID=8YFLogxK
M3 - Article
C2 - 6620416
AN - SCOPUS:0020609675
VL - 11
SP - 857
EP - 867
JO - Journal of Toxicology and Environmental Health
JF - Journal of Toxicology and Environmental Health
SN - 0098-4108
IS - 4-6
ER -