Effect of senescence on the bioactivation of aliphatic halides

A. B. DiRenzo, A Jay Gandolfi, I. G. Sipes, J. N. McDougal

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Since the toxicity of xenobiotics is often related to their metabolism, this study was concerned with the relationship between aging and the bioactivation and covalent binding of certain aliphatic halides to microsomal protein and lipid. Hepatic microsomes were isolated from control and phenobarbital induced young (4 mo), adult (11 mo) and senescent (27 mo) Fischer 344 rats. Bioactivation and subsequent covalent binding were studied with 14C-labeled 1,2-dibromoethane, carbon tetrachloride, trichloroethylene, and 1,1,2-trichloroethane. With control rats, level of binding increased slightly between 4 and 11 mo; however the values decreased 50-75% in the 27 mo group compared to the 11 mo group. No significant differences were noted between phenobarbital induced groups with regards to bioactivation of the aliphatic halides and their covalent binding to proteins and lipids. As an explanation for the decreased bioactivation ability in the senescent rats, they were also found to have significantly less hepatic cytochrome P-450 (-35%), NADPH cytochrome C reductase (-31%), and ethylmorphine N-demethylase activity (-43%) when compared to the 11 mo age group. These differences were reduced when comparisons were made between the various age groups of phenobarbital induced animals. This suppression may indicate a decreased potential for the expression of toxicities requiring bioactivation.

Original languageEnglish (US)
Pages (from-to)493-502
Number of pages10
JournalResearch Communications in Chemical Pathology and Pharmacology
Volume36
Issue number3
StatePublished - 1982

Fingerprint

Phenobarbital
Toxicity
Rats
Ethylmorphine-N-Demethylase
Age Groups
Ethylene Dibromide
Rat control
Cytochrome Reductases
Lipids
Trichloroethylene
Carbon Tetrachloride
Liver
Inbred F344 Rats
Xenobiotics
Cytochromes
Microsomes
NADP
Metabolism
Cytochrome P-450 Enzyme System
Carrier Proteins

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Effect of senescence on the bioactivation of aliphatic halides. / DiRenzo, A. B.; Gandolfi, A Jay; Sipes, I. G.; McDougal, J. N.

In: Research Communications in Chemical Pathology and Pharmacology, Vol. 36, No. 3, 1982, p. 493-502.

Research output: Contribution to journalArticle

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AB - Since the toxicity of xenobiotics is often related to their metabolism, this study was concerned with the relationship between aging and the bioactivation and covalent binding of certain aliphatic halides to microsomal protein and lipid. Hepatic microsomes were isolated from control and phenobarbital induced young (4 mo), adult (11 mo) and senescent (27 mo) Fischer 344 rats. Bioactivation and subsequent covalent binding were studied with 14C-labeled 1,2-dibromoethane, carbon tetrachloride, trichloroethylene, and 1,1,2-trichloroethane. With control rats, level of binding increased slightly between 4 and 11 mo; however the values decreased 50-75% in the 27 mo group compared to the 11 mo group. No significant differences were noted between phenobarbital induced groups with regards to bioactivation of the aliphatic halides and their covalent binding to proteins and lipids. As an explanation for the decreased bioactivation ability in the senescent rats, they were also found to have significantly less hepatic cytochrome P-450 (-35%), NADPH cytochrome C reductase (-31%), and ethylmorphine N-demethylase activity (-43%) when compared to the 11 mo age group. These differences were reduced when comparisons were made between the various age groups of phenobarbital induced animals. This suppression may indicate a decreased potential for the expression of toxicities requiring bioactivation.

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