Stimulation of DNA synthesis in primary rat hepatocyte cultures by liver tumor promoters: Interactions with other growth factors

Yasmin Anum Mohd Yusof, Anthony M. Edwards

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Mechanism(s) of tumor promotion in liver by xenobiotics such as hexachlorocyclohexane (HCH), 1,1,1-trichloro-2,2-bis (4-chlorophenyl)ethane (DDT) and phenobarbital (PB) are not understood in detail although growth-stimulatory effects may be significant in their action. As a basis for studying mechanisms of growth control by liver tumor promoters, effects of xenobiotics on DNA synthesis have been examined in primary cultures of normal rat hepatocytes, maintained under fully-defined conditions. The xenobiotics alone were relatively ineffective but they exhibited synergism with epidermal growth factor (EGF), insulin and dexamethasone in stimulating DNA synthesis and were effective in moderate-to-low density cultures but not in confluent monolayers. Under conditions optimized for HCH or pregnenolone 16α-carbonitrile (PCN) (i.e. subconfluent cultures exposed to insulin, EGF and dexamethasone), HCH, PCN, DDT or PB caused a transient stimulation of DNA synthesis, apparent after 2 days in culture. This probably reflected earlier entry of hepatocytes to S-phase. HCH was shown to increase total DNA, total numbers of nuclei and numbers of cells undergoing mitosis per culture. In optimized conditions, HCH or PCN were about additive with norepinephrine, dialyzed serum or pyruvate or with a small effect of tri-iodothyronine in stimulating DNA synthesis. Although conditions optimal for HCH or PCN were not necessarily optimal for detecting growth-stimulatory effects of other xenobiotics or steroids, these culture conditions were shown to support stimulation of DNA synthesis by a variety of known liver tumor promoters including barbiturates, estrogens, progestins, peroxisomal proliferators and bile acids. Several compounds known not to promote liver carcinogenesis failed to stimulate DNA synthesis in similar hepatocyte cultures.

Original languageEnglish
Pages (from-to)761-770
Number of pages10
JournalCarcinogenesis
Volume11
Issue number5
Publication statusPublished - May 1990
Externally publishedYes

Fingerprint

Growth Factors
Lindane
Promoter
Carcinogens
Liver
Rats
Tumors
Pregnenolone Carbonitrile
Hepatocytes
Tumor
Intercellular Signaling Peptides and Proteins
DNA
Synthesis
Xenobiotics
Interaction
DDT
Insulin
Phenobarbital
Epidermal Growth Factor
Dexamethasone

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Stimulation of DNA synthesis in primary rat hepatocyte cultures by liver tumor promoters : Interactions with other growth factors. / Mohd Yusof, Yasmin Anum; Edwards, Anthony M.

In: Carcinogenesis, Vol. 11, No. 5, 05.1990, p. 761-770.

Research output: Contribution to journalArticle

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