Aflatoxin toxicity in cultured human epidermal cells

Stimulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Agnes A. Walsh, Dennis P H Hsieh, Robert H. Rice

Research output: Contribution to journalArticle

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Abstract

Aflatoxin B1 (AFB1) at 1 μg/ml was markedly toxic to human epidermal cells grown in the Rheinwald-Green 3T3 feeder layer system. At 0.1 μg/ml, the toxicity was barely evident, as assessed by colony expansion during a 2 week exposure, but it was dramatically stimulated by 5 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which was non-toxic alone. Neither AFB1-dihydrodiol nor AFB2 were toxic in the presence or absence of TCDD, indicating that metabolism to the 8,9-epoxide was responsible for the AFB1 toxicity. Stimulation of AFB1 epoxidation by TCDD was also indicated by the >20-fold increase in DNA adduct formation in cultures exposed to [14C]AFB1 and TCDD for 4 days as compared to AFB1 alone. Analysis of free metabolites in culture medium by reverse-phase HPLC revealed that confluent epidermal cultures metabolized AFB1 to AFM1, AFB2a and aflatoxicol. In the presence of TCDD, the levels of AFM1 were higher (14 versus 3% of dose) as were those of AFB2a (3 versus 0.5% of dose), while aflatoxicol levels were lower (0.8 versus 2% of dose). In the absence of irradiated 3T3, the toxicities of AFB1, AFB2, AFM1 and aflatoxicol to cells in serum-free medium (0.15 mM Ca2+) were similar to those in the feeder layer system. Although this moderately low calcium concentration appeared quite satisfactory for observing toxicity, the response was attenuated at a lower calcium concentration (0.09 mM Ca2+).

Original languageEnglish (US)
Pages (from-to)2029-2033
Number of pages5
JournalCarcinogenesis
Volume13
Issue number11
StatePublished - Nov 1992

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Aflatoxins
Aflatoxin B1
Toxicity
Dose
Cell
Calcium
Feeder Cells
Poisons
High-performance Liquid Chromatography
Metabolism
Reverse
Fold
Epoxidation
DNA Adducts
Human
Polychlorinated Dibenzodioxins
Aflatoxin
Serum-Free Culture Media
Metabolites
Culture Media

ASJC Scopus subject areas

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

Cite this

Aflatoxin toxicity in cultured human epidermal cells : Stimulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin. / Walsh, Agnes A.; Hsieh, Dennis P H; Rice, Robert H.

In: Carcinogenesis, Vol. 13, No. 11, 11.1992, p. 2029-2033.

Research output: Contribution to journalArticle

Walsh, Agnes A. ; Hsieh, Dennis P H ; Rice, Robert H. / Aflatoxin toxicity in cultured human epidermal cells : Stimulation by 2,3,7,8-tetrachlorodibenzo-p-dioxin. In: Carcinogenesis. 1992 ; Vol. 13, No. 11. pp. 2029-2033.
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