No abstract

An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germfree Sprague-Dawley rats is maintained during periods of observation as ing as long as 7 months. The bacteria are found at levels exceeding 107 per g in the forestomach and at levels greater than 108 per g in the lower bowel and in the feces. Only approximately 104 bacteria per g are found in the posterior stomach and in the upper small intestine. The association of the salmonella mutants is maintained when the bacterial association is increased by the addition of other bacteria characteristic of the gastrointestinal flora. Carcinogenic amines, which cause strain TA1538 to revert to histidine independence in Ames' in vitro assays, increase the number of revertants in the feces when fed to the salmonella-associated rats. In contrast, the number of revertants in the feces does not increase when the rats are fed structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists. Sacrifice of rats after feeding the carcinogen 2-nitrofluorene indicates that the number of revertants is increased in the cecum and colon as well as in the feces. The apparent proximity of the bacterial mutagenic response to the location of the tumor response in the colon suggests that the rat associated with the histidine auxotroph may provide a useful model for further investigation of the possible association between bacterial mutagenesis and carcinogenesis within the gastrointestinal tract. In addition, with this model it may be possible to evaluate selectively the effects of various constituents of the flora on the activation of compounds provoking the revertant response.Concern about exposure to possible mutagenic and carcinogenic agents has stimulated the development of test systems to warn of the presence of such compounds in the environment. Since alterations in nucleic acids are the basis of mutagenesis, and possibly also of carcinogenesis (1), it seemed logical to test compounds in systems previously developed for bacterial genetics in which alterations in nucleic acid structure might be discerned on the basis of easily recognizable phenotypic alterations. Thus, alterations of DNA (2), the detection of mutations in bacteria (3) and phages (4), and the expression of prophages (5) have each served as the basis for identifying chemicals with mutagenic properties.

No abstract

An association of the histidine auxotroph of Salmonella typhimurium (strain TA1538) within the gastrointestinal tract of otherwise germ-free Sprague-Dawley rats is maintained during observations for up to 7 months. The bacteria exceed concentrations of 10(7)/g in the forestomach and exceed concentrations of 10(8)/g in the lower bowel and feces. When carcinogens are ingested, the number of revertants in the feces increases. The ingestion of structurally related compounds which are not mutagenic to the bacteria in vitro and for which no evidence of carcinogenicity exists does not increase the number of revertants in the feces. The numbers of salmonella are increased by the addition of Lactobacillus plantarum and Bacteroides fragilis but the salmonella disappear from the gastrointestinal tract when the rats are conventionalized. With the additional flora, there is a decrease in the number of revertants appearing in the feces in response to a given dose of carcinogen. This decrease may reflect an effect of the flora on the activity of the metabolic pathway responsible for the presence of the ultimate carcinogen or it may simply be an effect on the salmonella mutants themselves.