Effect of human gastric juice on the mutagenicity of chemicals.
10 mutagens were assayed in the Salmonella test after a pre-incubation step with human gastric juice. Such treatment affected the activity of 4 compounds, with different mechanisms, either in the sense of deactivation (sodium azide and sodium dichromate), of stabilization (captan), or even of potentiation (ICR-170). Conversely, the mutagenicity of other compounds (folpet, sodium nitrite, ICR-191, nitrofurantoin and a related drug) was unchanged. The stability of 2 carcinogens requiring metabolic activation, namely benzo[a]pyrene and aflatoxin B1, provided evidence that pre-incubation of compounds with gastric juice is compatible with the subsequent addition of liver post-mitochondrial preparations, thus reproducing in vitro 2 consecutive metabolic steps occurring in the organism. These findings lead us to report an improved correlation between assays in vivo and in vitro, in particular by explaining the lack of carcinogenicity of some mutagens introduced orally or by gastric intubation. Therefore, the Salmonella/gastric juice test is proposed as an additional assay for predicting the potential health hazards of chemicals.
D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005750:Gastric Juice / Q000378:metabolism*; D005821:Genetic Techniques; D006801:Humans; D009153:Mutagens / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics
D002273:Carcinogens; D009153:Mutagens