On mechanisms affecting species susceptibility to aflatoxin

Robert S. Portman, Kent Plowman, T. Colin Campbell

Research output: Contribution to journalArticle

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Abstract

1. 1. Use of mouse- and rat-liver slice preparations permitted a determination of the rates of transport of aflatoxin B1 into the cell followed by subsequent rates of metabolism of aflatoxin B1 to M1 by microsomal preparations. 2. 2. The acute toxicity-response difference between these species, as measured by the concentration required to caused cell death, is 2.1-fold; that is 2.1 times as much B1 is required to kill the mouse-liver cell, giving the mouse the advantage in resistance, in part due to faster metabolic rates and in part due to slower transport rates. 3. 3. A mathematical model based upon rates of transport and metabolism was developed in order to project internal B1 and M1 concentrations as functions of initial external B1 concentrations and/or exposure times. The maximum internal concentrations of B1 achieved just prior to cell death are 158 μM for the rat and 174 μM for the mouse. This small difference, in spite of the rather divergent initial extracellular concentrations generating them, indicates equivalence of these two species in terms of intracellular target-site sensitivity. 4. 4. The carcinogenic-response difference, as measured in the model by the half-life of decay of a small internal concentration developed over a short period of time, is 4.9-5.8-fold; that is, it takes 5-6 times longer for a given concentration (equivalent for each species) to be reduced to one-half its value in the rat as compared to the mouse, again giving the mouse the advantage. 5. 5. These experiments support the hypothesis that the rate of cellular transport is a considerably more important aspect of the pathological effects of affatoxin than the subsequent rate of metabolism and support the hypothesis that aflatoxin B1 has a much greater role in the toxic lesions than aflatoxin M1.

Original languageEnglish (US)
Pages (from-to)487-495
Number of pages9
JournalBBA - General Subjects
Volume208
Issue number3
DOIs
StatePublished - Jun 16 1970

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Aflatoxin B1
Aflatoxins
Metabolism
Rats
Cell death
Liver
Aflatoxin M1
Poisons
Toxicity
Cell Death
Mathematical models
Half-Life
Theoretical Models
Experiments

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology
  • Medicine(all)

Cite this

On mechanisms affecting species susceptibility to aflatoxin. / Portman, Robert S.; Plowman, Kent; Colin Campbell, T.

In: BBA - General Subjects, Vol. 208, No. 3, 16.06.1970, p. 487-495.

Research output: Contribution to journalArticle

Portman, RS, Plowman, K & Colin Campbell, T 1970, 'On mechanisms affecting species susceptibility to aflatoxin', BBA - General Subjects, vol. 208, no. 3, pp. 487-495. https://doi.org/10.1016/0304-4165(70)90223-0
Portman, Robert S. ; Plowman, Kent ; Colin Campbell, T. / On mechanisms affecting species susceptibility to aflatoxin. In: BBA - General Subjects. 1970 ; Vol. 208, No. 3. pp. 487-495.
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