Keratinocyte cell-mediated mutagenesis assay: Correlation with in vivo tumor studies

John J. Reiners, Larry P. Yotti, Catherine K. Mckeown, Stephen Nesnow, Thomas J Slaga

Research output: Contribution to journalArticle

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Abstract

A murine keratinocyte cell-mediated mutagenesis assay was characterized and examined as an in vitro model system for studying the biotransformation of promutagens/procarcinogens by mouse skin. The assay used living cultured newborn SENCAR keratinocytes for the metabolic activation of promutagens and Chinese hamster lung V-79 fibroblasts for detection of resulting mutagens. Mutations at, or affecting, the hypoxanthine-guanine phosphoribosyltransferase locus were scored by resisistance to 6-thioguanine. The relative mutagenicities of several polycyclic aromatic hydrocarbons (PAHs) in the cell-mediated assay correlated with the in vivo skin tumongenicity of the PAHs determined in a two-stage carcinogenesis protocol. Metabolic activation of the promutagenic PAHs to ultimate mutagens was dependent upon the presence of the cultured keratinocyte feeder layer. 7,8-Benzoflavone, a potent inhibitor of 7, 12-dimethylbenz- [a]anthracene (DMBA)-dependent initiation in mouse skin, inhibited DMBA-dependent mutagenesis in the cell-mediated assay in a concentration responsive manner. The non-PAH promutagens, dimethylnitrosamine (DMN) and sterigmatocystin (STC) were both activated by cultured keratinocytes to cytotoxic derivatives. DMN was neither mutagenic in the cell-mediated assay nor tumorigenic in mouse skin when tested in a two-stage carcinogenesis protocol. STC was weakly mutagenic and tumorigenic in mouse skin.

Original languageEnglish (US)
Pages (from-to)321-326
Number of pages6
JournalCarcinogenesis
Volume4
Issue number3
DOIs
StatePublished - 1983
Externally publishedYes

Fingerprint

Mutagenesis
Keratinocytes
Skin
Tumors
Tumor
Assays
Hydrocarbons
Mouse
Polycyclic Aromatic Hydrocarbons
Polycyclic aromatic hydrocarbons
Sterigmatocystin
Mutagens
Cell
Dimethylnitrosamine
9,10-Dimethyl-1,2-benzanthracene
Carcinogenesis
Neoplasms
Dependent
Activation
Chemical activation

ASJC Scopus subject areas

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

Cite this

Keratinocyte cell-mediated mutagenesis assay : Correlation with in vivo tumor studies. / Reiners, John J.; Yotti, Larry P.; Mckeown, Catherine K.; Nesnow, Stephen; Slaga, Thomas J.

In: Carcinogenesis, Vol. 4, No. 3, 1983, p. 321-326.

Research output: Contribution to journalArticle

Reiners, John J. ; Yotti, Larry P. ; Mckeown, Catherine K. ; Nesnow, Stephen ; Slaga, Thomas J. / Keratinocyte cell-mediated mutagenesis assay : Correlation with in vivo tumor studies. In: Carcinogenesis. 1983 ; Vol. 4, No. 3. pp. 321-326.
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