PubMed Health⌕ Search

Biomedical subjects

A J Garro

Publications and source records attributed to A J Garro.

At least 19 recordsLinked to original sources
PubMed1991

Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome.

Acute ethanol administration (3 g/kg twice a day) to pregnant mice, from the 9th thru the 11th day of gestation, resulted in hypomethylation of fetal deoxyribonucleic acid (DNA). Nuclei isolated from the fetuses of the ethanol-treated mice had lower levels of methylase activity relative to controls even in the presence of excess S-adenosylmethionine, which serves as the methyl donor for the enzyme DNA methyltransferase. Acetaldehyde, at concentrations as low as 3 to 10 microM, inhibited DNA methyltransferase activity in vitro. Since DNA methylation is thought to play an important role in the regulation of gene expression during embryogenesis, ethanol-associated alterations in fetal DNA methylation may contribute to the developmental abnormalities seen in the fetal alcohol syndrome.

5-Methylcytosine↗
PubMed1989

Mutagenic activity in gastric juice and urine of subjects with chronic atrophic gastritis, gastric epithelial dysplasia and gastric cancer.

Gastric juice and urine samples from consecutive patients who underwent endoscopy for upper GI tract complaints were examined for the presence of mutagens. Patients endoscopically and histologically diagnosed as having either chronic atrophic gastritis (CAG) or gastric cancer (GC) had higher than normal levels of mutagens in their gastric juice and urine. The gastric juice pH of these patients was also elevated and, in the case of the CAG patients, contained detectable levels of nitrites. No correlation was however found between gastric mutagen levels and urinary mutagen excretion in the individuals examined.

Adult↗
PubMed1989

Effects of chronic ethanol consumption on carcinogen activating and detoxifying systems in rat upper alimentary tract tissue.

The effect of chronic ethanol consumption on enzyme systems directly involved in carcinogen activation and detoxification were studied in rat upper alimentary tract tissue. Microsomal cytochrome P-450 (P-450) levels and glutathione levels as well as glutathione transferase and UDP-glucuronic acid transferase (UDPGT) activities were measured in mucosa scraped from esophagus, forestomach and glandular stomach of rats which had been pair-fed ethanol or dextrimaltose-containing diets. Esophageal and forestomach P-450 levels were increased in the ethanol-fed rats. The ethanol diet also produced a small but significant increase in esophageal glutathione transferase levels. Glutathione levels and UDPGT activity were unaffected. Since P-450 is directly involved in the activation of many chemical carcinogens, these results are consistent with the hypothesis that the increase in upper alimentary tract cancer risk associated with alcohol abuse is due, at least in part, to ethanol's altering the balance between carcinogen activation and detoxification.

Alcohol Drinking↗
PubMed1988

Chronic ethanol consumption inhibits repair of dimethylnitrosamine-induced DNA alkylation.

Chronic ethanol consumption causes a DNA repair deficiency. This was demonstrated in Sprague-Dawley rats injected with 14C-labeled dimethylnitrosamine after being pair-fed isocaloric, ethanol, or carbohydrate control diets for 4 weeks. Hepatic DNA was isolated from rats killed at intervals over a 36 hour period after administration of the nitrosamine and concentrations of alkylated guanine derivatives were measured. While N7-methylguanine was lost at equivalent rates from the DNA of both diet groups, 06methylguanine, a promutagenic lesion, persisted at higher levels for longer periods of time in the DNA from the alcohol-fed animals.

Alcoholism↗
PubMed1988

In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase.

Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase, which like O6MeGT have cysteines in their active sites, were not inhibited by acetaldehyde at the levels that inhibited O6MeGT. Disulfiram, an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitory effect of ethanol in vivo. These results indicate that the inhibitory effect of ethanol on O6MeGT activity is mediated primarily via its metabolite, acetaldehyde.

Acetaldehyde↗
PubMed1986

The effects of chronic ethanol consumption on carcinogen metabolism and on O6-methylguanine transferase-mediated repair of alkylated DNA.

This article presents a review and update of recent experiments conducted in collaboration with Dr. C. S. Lieber on mechanisms underlying the increased cancer risk associated with alcohol abuse. Ethanol has been found to be a potent inducer of microsomal enzymes involved in carcinogen metabolism in a variety of rat tissues including liver, esophagus, lungs, and intestines. In some of these tissues, ethanol's inductive effect on microsomal cytochrome P-450 enzyme activity may result in enhanced levels of electrophilic metabolites of procarcinogens which are not readily detoxified. In addition, chronic ethanol feeding has been found to depress the activity of O6-methylguanine transferase, an enzyme involved in the repair of carcinogen-induced DNA alkylation. The effects of ethanol on carcinogen metabolism and on DNA repair would be expected to enhance the initiation phase of chemically induced cancers.

Alcoholism↗
PubMed1985

Nucleotide sequence of the immunity region of Bacillus subtilis bacteriophage phi 105: identification of the repressor gene and its mRNA and protein products.

A gene involved in the regulation of lysogeny in the temperate Bacillus subtilis phage phi 105 has been identified and isolated. A plasmid, pDC4, was constructed that contains a 740-bp HindIII-PvuII fragment that is derived from the phi 105 immunity region and is capable of rendering B. subtilis immune to infection by phi 105. Three different hybrid plasmids that contain the 740-bp fragment, pAG101 [Cully and Garro, J. Virol. 34 (1980) 789-791], pDC1 and pDC2, were found to synthesize a common 18-kDal polypeptide in B. subtilis minicells and Escherichia coli maxicells. The nucleotide (nt) sequence of this region revealed three open reading frames (ORFs) that predict proteins with Mrs of 16521, 7332, and 5516. In vivo synthesized phi 105 prophage RNA was mapped by primer extension and shown to be transcribed from the DNA strand coding for the Mr 16521 protein. The 5' end of the phi 105 lysogen RNA was mapped to a region that contains conserved sequences for RNA polymerase recognition.

Amino Acid Sequence↗
PubMed1979

Bacterial fusion assayed by a prophage complementation test.

In previous studies of bacterial protoplast fusion, only the frequencies of cell wall regeneration and of bacterial recombination were determined. In this work the frequency of the heterozygous fusion products is measured by prophage complementation. Two multiply marked nonsuppressing strains of Bacillus subtilis, each lysogenic for a different Sus mutant of the phage phi 105, were induced by mitomycin C, protoplasted, fused, and, after dilution in hypertonic broth, incubated until plating with phi 105-sensitive indicator bacteria. When cell lysis was avoided, the frequency of the heterozygous fused cells could be determined from the number of infectious centers produced. The very high frequencies observed are in good agreement with those determined directly, with nonlysogenic strains, by electron microscopic examination of the fused protoplasts (C. Frehel, A. M. Lheritier, C. Sanchez-Rivas, and P. Schaeffer, J. Bacteriol. 137:1354--1361, 1979). Evidence is presented that fusion occurs in two steps, one polyethylene glycol dependent, the other energy requiring. The bacterial growth medium affects the ability of the protoplasts to fuse and to regenerate a cell wall. When experiments using different growth media were compared, an inverse relationship between these abilities was observed, and a direct relationship appeared between the heterozygotes (corrected for wall regeneration) and the recombinant bacteria that were found.

Bacillus subtilis↗
PubMed1979

Alcohol-related diseases and carcinogenesis.

Possible mechanisms whereby alcohol abuse and alcohol-related diseases may promote the development of cancer are analyzed. The mechanisms discussed include: (a) contact-related local effects on the upper gastrointestinal tract; (b) the presence of low levels of carcinogens in alcoholic beverages; (c) induction of microsomal enzymes involved in carcinogen metabolism; (d) various types of cellular injury produced by ethanol and its metabolites and their relationship to cancer, particularly in the liver; (e) the nutritional disturbances frequently associated with alcohol abuse. The relationship between alcohol-induced cirrhosis and hepatocellular carcinoma is also discussed, and case histories of patients seen at the Bronx Veterans Administration Medical Center with hepatocellular carcinoma in the absence of cirrhosis are reviewed. Data are presented demonstrating the induction, by chronic ethanol consumption, of microsomal enzymes which convert procarcinogens to carcinogens. These data were derived from experiments in which the ability of microsomes isolated from liver, intestine, and lung tissues of ethanol-fed and control rats to activate several test carcinogens was examined in the Ames Salmonella-mutagenicity test. The hypothesis is presented that ethanol-mediated induction of enzyme systems which activate procarcinogens to carcinogens in various tissues contributes to the enhanced incidence of cancer in the alcoholic.

Alcoholism↗
PubMed1978

Correlated genetic and EcoRI cleavage map of Bacillus subtilis bacteriophage phi105 DNA.

The seven previously identified EcoRI cleavage fragments of phi 105 DNA were ordered with respect to their sites of origin on the phage genome by marker rescue. One fragment, H, did not carry any determinants essential for replication. This fragment was totally missing in a deletion mutant which exhibited a lysogenization-defective phenotype. There is a nonessential region on the phi 105 genome which begins in fragment B, spans fragment H, and ends in fragment F. The size of the nonessential region, as estimated by alterations observed in the fragmentation patterns of deletion mutant DNAs, is approximately 2.7 X 10(6) daltons. Two new EcoRI cleavage fragments with molecular weights of approximately 0.2 X 10(6) were detected by autoradiography of 32P-labeled DNA. These small fragments were not located on the cleavage map.

Bacillus subtilis↗
PubMed1977

Fragmentation of Bacillus bacteriophage phi105 DNA by complementary single-stranded DNA in the cohesive ends of the molecule.

The structure of DNA from the temperate Bacillus subtilis phage phi105 was examined by using the restriction endonuclease EcoRI and by sedimentation analysis. The DNA contains six EcoRI cleavage sites. Although eight DNA fragments were identified in the EcoRI digests, the largest of these was shown to consist of the two fragments that carry the cohesive ends of the phage DNA. In neutral gradients, the majority of whole phi105 DNA sedimented as nicked circles and the remainder as oligomers. No unit-length linear structures were detected. The associated cohesive ends could be sealed by DNA ligase from Escherichia coli and could be cleaved by S1 nuclease. On the basis of these results and previously reported studies, it appears that, as isolated from phage particles, phi105 DNA is a circular molecule that is formed from the linear structure by the association of complementary single-stranded DNA.

Bacillus subtilis↗