Mutagenicity of primary and secondary carcinogens altered by normal and induced hepatic microsomes.
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Biomedical subjects
Publications and source records attributed to A J Garro.
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A genetic marker responsible for the killing activity of PBSX, a defective phage carried by Bacillus subtilis 168, has been located on the bacterial chromosome. Two mutant strains of B. subtilis 168, which produced tailless phage particles upon mitomycin C induction, were shown to carry lesions, designated xtl-1 and xtl-2, which were linked by transformation and PBS1-mediated transduction to metC. The link-age relationship between xtl and adjacent auxotrophic markers was determined by three-factor PBS1 transduction, the suggested order of markers being argO 1 metA metC xtl.
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We investigated the effect of chronic ethanol feeding on the EGF receptor in rat stomach. Adult male rats were fed either an isocaloric control or ethanol (EtOH)-containing liquid diet (36% total calories as EtOH) for 4 weeks EtOH significantly reduced the specific binding of 125I-EGF to the gastric mucosal membrane (control vs. EtOH, 2.07 +/- 0.2 vs. 0.94 +/- 0.16 fmol/mg protein; p < 0.01). Scatchard analysis suggested that the lower binding might be due to the reduction of EGF receptor number, and/or the affinity of the high-affinity binding site. Western blot analysis, using anti-EGF receptor antibody, revealed four immunoreactive protein bands (180, 150, 60, and 50 kDa) in the lectin-purified gastric membrane prepared from both groups. However, the intensities of these protein bands in the EtOH-fed animals were 90% lower compared to the controls. In the EGF-responsive protein kinase assay, 32P-ATP was incubated with lectin-purified samples in the absence or presence of 1 microM EGF. EGF stimulated autophosphorylation of the EGF receptor (180 kDa) in stomach from the control groups, but not the EtOH-fed animals. This EtOH-related alteration of the gastric EGF receptor may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.
Tissues derived from male Sprague-Dawley rats which had been pair-fed isocaloric ethanol or carbohydrate control diets for 4 weeks were used to determine the effect of chronic ethanol exposure on the activation of the smoking and diet-associated procarcinogen nitrosopyrrolidine (NPY). Microsomal preparations from lungs and liver and S9 fractions from alimentary tract mucosa were tested for their capacity to activate NPY to a mutagen by the Ames Salmonella assay. Chronic ethanol exposure resulted in an increased capacity to activate NPY by microsomes derived from liver, lungs, and esophagus but not from stomach. The three tissues in which enhanced activation of NPY was observed in the present study also have been noted in epidemiological studies to be target sites of alcohol abuse-associated increased cancer risk. The results presented here suggest that dietary ethanol's effect on carcinogen metabolism may be responsible, at least in part, for the increased cancer risk observed in chronic alcohol abusers.