TY - JOUR
T1 - In vivo and in vitro nephrotoxicity of the cysteine conjugate of hexachlorobutadiene
AU - Jaffe, Deborah R.
AU - Hassall, Christopher D.
AU - Brendel, Klaus
AU - Gandolfi, A. Jay
PY - 1983/1/1
Y1 - 1983/1/1
N2 - Hexachlorobutadiene (HCBD), a renal toxin and carcinogen, is thought to require bioactivation to exert toxicity. The chemically synthesized cysteine conjugate of structurally simitar haiogenated hydrocarbons, trichloroethylene, chlorotrifluoro- ethylene, and chlorodifluoroethylene, have been shown to be nephrotoxic. Hence the cysteine conjugate of HCBD, S-pentachlorobuta-l,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 1O-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 mgjkg ip). Genotoxicity in renal tissue was studied by using alkaline elution to detect DNA singlestrand 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 I0-3 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 simitar haiogenated hydrocarbons, trichloroethylene, chlorotrifluoro- ethylene, and chlorodifluoroethylene, have been shown to be nephrotoxic. Hence the cysteine conjugate of HCBD, S-pentachlorobuta-l,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 1O-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 mgjkg ip). Genotoxicity in renal tissue was studied by using alkaline elution to detect DNA singlestrand 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 I0-3 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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U2 - 10.1080/15287398309530389
DO - 10.1080/15287398309530389
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 -