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Effects of age, species difference, antibiotics and toxicants on intestinal enzyme activity and genotoxicity
Author(s) -
Chadwick R. W.,
George S. E.,
Kohan M. J.,
Allison J. C.,
Chang J.,
Long J. E.,
Duffy M. C.,
Dekker J. P.,
Forehand L. R.
Publication year - 1993
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620120804
Subject(s) - pentachlorophenol , genotoxicity , enzyme , biotransformation , antibiotics , xenobiotic , chemistry , lindane , enzyme assay , toxicity , nitroreductase , gastrointestinal tract , pharmacology , biochemistry , biology , microbiology and biotechnology , environmental chemistry , pesticide , ecology , organic chemistry
Altered intestinal enzyme activity significantly affects the biotransformation and toxicity of many xenobiotics. This article summarizes research, supported by the U.S. Air Force Bioenvironmental Hazards Research Program, that employs a novel gas‐liquid chromatographic assay to investigate the effects of age, species difference, antibiotics, and environmental chemicals on enzyme activity in various regions of the intestinal tract. Significant research findings include the following: (a) age‐dependent alterations in enzyme activity in the gastrointestinal (GI) tract of the developing animal that suggest a changing susceptibility to toxicants during this period; (b) discovery of previously unreported mucosal enzymes in the small intestine that are present in germ‐free rats and are not susceptible to antibiotics; (c) markedly greater intestinal nitroreductase activity and significantly higher bioactivation of the procarcinogen 2,6‐dinitrotoluene (DNT) in CD‐1 mice than in Fischer 344 rats; (d) significantly altered intestinal enzyme activity in rats pretreated with lindane, pentachlorophenol, 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T), or Aroclor 1254; (e) potentiated DNT genotoxicity by Aroclor 1254 and pentachlorophenol pretreatment; and (f) a transient antagonism of DNT genotoxicity by 2,4,5‐T pretreatment. Enzyme activity in the small intestine may have greater toxicological importance than previously thought in the biotransformation of environmental chemicals and as an indicator of change in the microbial flora.