Diet, DDT, and the toxicity of drugs and chemicals.
The toxic and carcinogenic effects of many compounds depend on their activation to reactive molecules in the cytochrome P-450 system of the endoplasmic reticulum of cells. Changes in dietary input alter P-450 levels in different tissues and so alter toxicity. In this way, low protein diets protect against carbon tetrachloride poisoning. Fats, proteins, and nonnutrients such as flavones, antioxidants, and contaminants like DDT all affect P-450 levels. The activated molecules may be diverted from their target sites by inactivation processes, such as epoxide hydratase or glutathione trappin. This is also under nutritional control. Low protein diets render animals sensitive to acetaminophen by reducing glutathione levels. In the sequence of events leading from initial contact of toxin with organism to eventual cell injury or neoplasm, nutritional factors are of import at every stage. Assessments of the toxicity of chemicals that do not take into account the nutritional variable in man are likely to be incorrect.
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000517:prevention & control; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003634:DDT / Q000494:pharmacology; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism; D004777:Environment; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011488:Protein Deficiency / Q000503:physiopathology; D012643:Selenium / Q000502:physiology; D014116:Toxicology; D014811:Vitamin E Deficiency / Q000503:physiopathology
D002273:Carcinogens; D004041:Dietary Fats; D004364:Pharmaceutical Preparations; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; D005978:Glutathione; D012643:Selenium