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Biomedical subjects

C Bernstein

Publications and source records attributed to C Bernstein.

At least 55 records · Page 3Linked to original sources
PubMed1992

Bile salt/acid induction of DNA damage in bacterial cells: effect of taurine conjugation.

Bile salts and acids have been implicated in the etiology of colon cancer, possibly through their ability to cause DNA damage. Taurine-conjugated and nonconjugated forms of three bile salts and one bile acid were tested for DNA repair-inducing potential and for cellular toxicity in a recently developed Escherichia coli chromotest system. The taurine-conjugated forms of sodium deoxycholate and lithocholic acid had reduced ability to induce DNA repair. Also the taurine-conjugated form of lithocholic acid had a reduced lethal effect. These observations suggest that the biotransformation step, whereby bacteria in the intestine remove the taurine added to bile salts in the liver, may be significant in the etiology of colon cancer.

Bile Acids and Salts↗
PubMed1992

A pilot study of steroid withdrawal followed by oral acyclovir in the treatment of chronic type B hepatitis.

Ten patients with chronic type B hepatitis were treated for four weeks with a rapidly tapered dose of oral prednisone (initial dose, 40 mg/d) followed by two weeks of no therapy followed by four weeks of oral acyclovir (600 mg/d). Liver biochemistry, HBsAg, HBeAg, DNA-polymerase and HBV-DNA levels in serum were determined prior to, during and for six months following therapy. The mean age +/- SD of the study population was 33 +/- 15 years (range 18-58). Nine of the patients were male. Four patients were Caucasian and six of Southeast Asian origin. Three patients were homosexual, all HIV antibody negative. The mean ALT level prior to treatment was 89 +/- 62 IU/L (range: 30-214). During the six month post-treatment follow-up period, 5/8 (63%) patients became DNA-P negative and 6/10 (60%) HBV-DNA negative. One responder reverted to DNA-P positive (final response, 50%) and another to HBV-DNA positive (final response, 50%) prior to completion of the study. Patients were more likely to become DNA-P or HBV-DNA negative if they had elevated pre-treatment ALT values and low levels of DNA-P and HBV-DNA. HBeAg became undetectable in 3/10 (30%) individuals, one of whom reverted to positive at the end of the follow-up period (final response, 20%). All patients remained HBsAg positive. Mild fatigue, which occurred in four individuals, was the most common side effect. The results of this study suggest that a controlled clinical trial of oral prednisone/acyclovir is warranted in the treatment of adults with chronic type B hepatitis.

Acyclovir↗
PubMed1991

Bile salt/acid induction of DNA damage in bacterial and mammalian cells: implications for colon cancer.

Two bile salts, sodium chenodeoxycholate and sodium deoxycholate, induced a DNA repair response in the bacterium Escherichia coli. Similarly, a bile acid and a bile salt, chenodeoxycholic acid and sodium deoxycholate, induced DNA repair (indicated by unscheduled DNA synthesis) in human foreskin fibroblasts. Also, DNA repair-deficient Chinese hamster ovary (CHO) cells were found to be more sensitive than normal cells to killing by bile salts. In particular, mutant UV4 CHO cells, defective in DNA excision repair and DNA cross-link removal, were more sensitive to sodium chenodeoxycholate, and mutant EM9 CHO cells, defective in strand-break rejoining, were more sensitive to sodium deoxycholate than wild-type cells. These results indicate that bile salts/acid damage DNA of both bacterial and mammalian cells in vivo. Previous epidemiological studies have shown that colon cancer incidence correlates with fecal bile acid levels. The findings reported here support the hypothesis that bile salts/acids have an etiologic role in colon cancer by causing DNA damage.

Animals↗
PubMed1989

Sexual reproduction as a response to H2O2 damage in Schizosaccharomyces pombe.

Although sexual reproduction is widespread, its adaptive advantage over asexual reproduction is unclear. One major advantage of sex may be its promotion of recombinational repair of DNA damage during meiosis. This idea predicts that treatment of the asexual form of a facultatively sexual-asexual eucaryote with a DNA-damaging agent may cause it to enter the sexual cycle more frequently. Endogenous hydrogen peroxide is a major natural source of DNA damage. Thus, we treated vegetative cells of Schizosaccharomyces pombe with hydrogen peroxide to test if sexual reproduction increases. Among untreated stationary-phase S. pombe populations the sexual spores produced by meiosis represented about 1% of the total cells. However, treatment of late-exponential-phase vegetative cells with hydrogen peroxide increased the percentage of meiotic spores in the stationary phase by 4- to 18-fold. Oxidative damage therefore induces sexual reproduction in a facultatively sexual organism, a result expected by the hypothesis that sex promotes DNA repair.

DNA Repair↗
PubMed1989

Recurrent bronchial carcinoid tumor.

Bronchial carcinoid tumors are considered to be of low grade malignancy, and if completely resected, to be cured. A patient with resection of a bronchial carcinoid presented 18 years later with superior vena caval obstruction, and carcinoid syndrome due to a recurrence. There was an excellent response to radiation.

Adult↗
PubMed1989

Water flow in the toad urinary bladder in response to vasopressin: role of potassium.

In agreement with previous reports, we found that absence of K+ from the serosal bath of the toad urinary bladder substantially impairs vasopressin and cAMP-stimulated water flow. The decreased response to vasopressin appears unrelated to prostaglandin production since inhibition of endogenous prostaglandins by pretreatment with naproxen 10(-5) M failed to prevent the effect seen with K+-free Ringer's. The resistance to vasopressin does not appear to be directly related to epithelial K+ concentrations, in that maneuvers leading to decreased intracellular K+ failed to produce a similar effect. A more likely explanation appears to be that K+-free Ringer's induces an increased cytosolic Ca++ which, in turn, decreases the hydrosmotic effects of vasopressin. Several lines of evidence argue in favor of such an explanation: (a) Increased cytosolic Ca++ had been found in other tissues with low extracellular K+; (b) The resistance to vasopressin decreases with decreased serosal Ca++; (c) The effects of K+-free Ringer's are not additive in situations believed to have increased epithelial Ca++, i.e. replacement of serosal Na+ with choline; (d) The effects of K+-free serosal bathing medium could be both prevented and/or reversed if already established by increasing serosal bath, and presumably intracellular, pH, which is believed to decrease intracellular Ca++.

Animals↗
PubMed1987

Recombinational repair of hydrogen peroxide-induced damages in DNA of phage T4.

Recently, hydrogen peroxide and its free-radical product, the hydroxyl radical (OH.) have been identified as major sources of DNA damage in living organisms. They occur as ubiquitous metabolic by-products and, in humans, cause several thousand damages in a cell's DNA per day. They are thought to be a major source of DNA damage leading to aging and cancer in multicellular organisms. This raises two questions. First, what pathways are used in repair of DNA damages caused by H2O2 and OH.? Second, a new theory has been proposed that sexual reproduction (sex) evolved to promote repair of DNA in the germ line of organisms. If this theory is correct, then the type of repair specifically available during the sexual process should be able to deal with important natural lesions such as those produced by H2O2 and OH. . Does this occur? We examined repair of hydrogen peroxide damage to DNA, using a standard bacteriophage T4 test system in which sexual reproduction is either permitted or not permitted. Post-replication recombinational repair and denV-dependent excision repair are not dependent on sex. Both of these processes had little or no effect on lethal H2O2 damage. Also, an enzyme important in repair of H2O2-induced DNA damage in the E. coli host cells, exonuclease III, was not utilized in repair of lethal H2O2 damage to the phage. However, multiplicity reactivation, a recombinational form of repair depending on the sexual interaction of two or more of the bacteriophage, was found to repair lethal H2O2 damages efficiently. Our results lend support to the repair hypothesis of sex. Also the homology-dependent recombinational repair utilized in the phage sexual process may be analogous to the homology-dependent recombination which is widespread in diploid eucaryotes. The recombinational repair pathway found in phage T4 may thus be a widely applicable model for repair of the ubiquitous DNA damage caused by endogenous oxidative reactions.

DNA↗
PubMed1978

Recombinational repair of alkylation lesions in phage T4. I. N-methyl-N'-nitro-N-nitrosoguanidine.

Treatment of phage T4-host adsorption complexes by MNNG increased recombination between two rII markers by about three-fold. Temperature sensitive mutants defective in genes 32, 46 and 47, which cause reductions in recombination at semirestrictive temperature, proved to be substantially more sensitive to MNNG at such temperatures than wild-type phage. In addition, the recombination defective mutants xm(uvsX) and y10(y) were sensitive to MNNG than wild-type, whereas mutants defective in genes 45 and denV, which are apparently not involved in recombination, were not MNNG sensitive. These findings suggest that a recombination pathway involving the products of genes 32, 46, 47, uvsX and y is employed in repairing MNNG-induced lethal lesions. This mechanism is effective in cells infected by single phage, implying post-replication recombinational repair between daughter chromosomes. MNNG-induced lesions are subjects to multiplicity reactivation, but mutants defective in genes 46 to 47 showed the same degree of multiplicity reactivation as wild-type phage. The gene 32 and gene 47 recombination defective mutants were tested for their effects of MNNG-induced reversion of an rII marker. No reduction in induced reversion was found. Thus, it appears that the postulated recombinational repair pathway employing the products of genes 32 and 47 does not contribute substanitally to induced mutagenesis.

Alkylation↗
PubMed1978

Recombinational repair of alkylation lesions in phage T4. II. Ethyl methanesulfonate.

Treatment of bacteriophage T4 by ethyl methanesulfonate (EMS) caused more than a doubling in recombination between two rII markers. The functions of genes 47, 46, 32, 30, uvsX and y are known to be required for genetic recombination, and mutants defective in these genes were found to be more sensitive to inactivation by EMS than wild-type phage. This suggests that a recombinational pathway involving the products of these genes may be employed in repairing EMS induced lethal lesions. Genes 45 and denV are apparently not involved in recombination, and mutants defective in these genes were not EMS-sensitive. Gene 47, 46 and y mutants which were defective in the repair of EMS induced lethal lesions had no detectable deficiency in their ability to undergo EMS-induced mutation. This implies that recombinational repair of EMS lesions does not contribute substantially to EMS mutagenesis. The results obtained here with EMS are general similar to the results reported in the preceding paper with MNNG, suggesting that the lesions caused by both of these monofunctional alkylating agents may be eliminated by similar recombinational repair processes.

Alkylation↗
PubMed1976

The dependence of HNO2 mutagenesis in phage T4 on ligase and the lack of dependence of 2AP mutagenesis on repair functions.

A temperature sensitive ligase allele of phage T4 reduced or eliminated HNO2 induced reversion of am mutants. Since at the temperatures used, the ligase mutant is defective in the repair of some types of lethal lesions (i.e., UV, MMS and EMS induced lesions) these results indicate that HNO2 mutagenesis may occur through a ligase dependent repair pathway. In contrast, 2AP induced mutation was not inhibited by mutants defective in the gene 30 ligase or in genes 32, 39, 41, 42, 44, 45, 46, 47, 49, 52, 56, 58-61 and v. This indicates that 2AP mutagenesis probably does not depend on a repair pathway in phage T4.

2-Aminopurine↗