Selective inhibition of liver-cell proliferation by CFT 1201 and SKF 525 A

Studies on growth processes induced by drugs and by partial hepatectomy
  • R. Schulte-Hermann
  • I. Schlicht
  • W. Koransky
  • C. Leberl
  • C. Eulenstedt
  • M. Zimek
Article

Summary

Of the xenobiotic compounds which are known to induce liver growth some are substrates of hepatic microsomal mixed-function oxidase. The aim of the present study was to check on whether normal functioning of this enzyme system is a prerequisite for growth induction by α-HCH***, BHT, and phenobarbital. Several biochemical and morphological tests were used to determine the degree of hyperplasia and hypertrophy induced in rat liver by these drugs, with and without concomitant application of two inhibitors of microsomal mixed-function oxidase: SKF 525 A and CFT 1201.

In the case of α-HCH, CFT 1201 prevents the hyperplastic but not the hypertrophic response of rat liver to the drug: augmentation of DNA content, enhanced incorporation of 3H-thymidine into DNA, increased mitotic rate, and increase in the number of nuclei synthesizing DNA all fail to occur while organ weight still increases. The same type of interference is seen with the growth-inducing effects of BHT and phenobarbital. SKF 525 A likewise inhibits cell proliferation induced by α-HCH.

In contrast, CFT 1201 does not block cell proliferation in response to partial hepatectomy or to hepatocellular damage produced by thioacetamide, nor does it inhibit the hyperplastic response of rat liver to high doses of isoproterenol.

It is concluded, therefore, that CFT 1201 does not interfere with processes essential for hepatocyte replication but rather acts selectively if induction of the replicative process is triggered by certain drugs. The nature of the CFT 1201-sensitive step is discussed.

Key words

Drug-Induced Liver Growth Liver Hyperplasia Cytochrome P450 Inhibitors SKF 525 A, CFT 1201 Prereplicative Phase 

Abbreviations

α-HCH

α-1,2,3,4,5,6-hexachlorocyclohexane = α-benzenehexachloride

CFT 1201

β-diethylaminoethylphenyldiallylacetate · HCl

SKF 525 A

β-diethylaminoethyldiphenylpropylacetate · HCl

BHT

3,5-di-tert.-butyl-4-hydroxytoluene

TAA

thioacetamide

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Copyright information

© Springer-Verlag 1972

Authors and Affiliations

  • R. Schulte-Hermann
    • 1
    • 2
  • I. Schlicht
    • 1
    • 2
  • W. Koransky
    • 1
    • 2
  • C. Leberl
    • 1
    • 2
  • C. Eulenstedt
    • 1
    • 2
  • M. Zimek
    • 1
    • 2
  1. 1.Institut für Toxikologie und Pharmakologie der Philipps-Universität MarburgMarburgGermany
  2. 2.Medizinische Klinik und Poliklinik des Klinikum Westend der Freien Universität BerlinBerlinGermany

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