2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice

TY - JOUR

T1 - 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice

AU - Sparrow, Barney R.

AU - Thompson, Cynthia S.

AU - Ryu, Byung‐Woo ‐W

AU - Selevonchick, Daniel P.

AU - Schaup, Henry W.

PY - 1994/12

Y1 - 1994/12

N2 - A dose‐dependent reduction of hepatic pyruvate carboxylase levels and activity occurs in C57BL/6J male mice given 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) i.p. in a corn oil carrier. The dose range was from 1 to 75 μg/kg body weight and the analysis was done 8 days postinjection. At the maximum TCDD level investigated, we found a 10‐fold reduction in pyruvate carboxylase activity. Furthermore, TCDD at a dose of 1 μg/kg body weight blocks corn oil induction of an increase in the amount of pyruvate carboxylase in liver protein extracts. At doses beyond those required to initiate a reduction in pyruvate carboxylase, lactate dehydrogenase isozyme patterns shift. This is accompanied by an increase in blood lactic acid levels. We propose that TCDD‐mediated reduction in pyruvate carboxylase and lactate dehydrogenase isozyme shifts may represent a major component in TCDD toxicity.

AB - A dose‐dependent reduction of hepatic pyruvate carboxylase levels and activity occurs in C57BL/6J male mice given 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) i.p. in a corn oil carrier. The dose range was from 1 to 75 μg/kg body weight and the analysis was done 8 days postinjection. At the maximum TCDD level investigated, we found a 10‐fold reduction in pyruvate carboxylase activity. Furthermore, TCDD at a dose of 1 μg/kg body weight blocks corn oil induction of an increase in the amount of pyruvate carboxylase in liver protein extracts. At doses beyond those required to initiate a reduction in pyruvate carboxylase, lactate dehydrogenase isozyme patterns shift. This is accompanied by an increase in blood lactic acid levels. We propose that TCDD‐mediated reduction in pyruvate carboxylase and lactate dehydrogenase isozyme shifts may represent a major component in TCDD toxicity.

KW - 2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin

KW - Lactate Dehydrogenase

KW - Pyruvate Carboxylase

KW - TCDD

UR - https://www.scopus.com/pages/publications/0028675554

U2 - 10.1002/jbt.2570090608

DO - 10.1002/jbt.2570090608

M3 - Article

C2 - 7891369

SN - 0887-2082

VL - 9

SP - 329

EP - 335

JO - Journal of Biochemical Toxicology

JF - Journal of Biochemical Toxicology

IS - 6

ER -