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Biomedical subjects

G T Bryan

Publications and source records attributed to G T Bryan.

At least 37 records · Page 2Linked to original sources
PubMed1988

Recontacting subjects in mutagen-exposure-monitoring studies: II. Results of a questionnaire study of mutagenesis researchers, with review of the pertinent literature.

A questionnaire on the attitudes of mutagenesis researchers regarding the health significance of and the use of data from tests of human mutagen exposure or genetic damage was completed by 71 of 312 (23%) individuals who had been participants in meetings or organizations concerned with mutagenesis research. On a point scale of 0 to 10, with 0 indicating strong disagreement, 5 indicating uncertainty, and 10 indicating strong agreement, the average respondent felt (8.31 +/- 2.27) that data indicating a probable health hazard should be shared automatically with the subjects, but was also moderately concerned about psychological distress of subjects learning of study results indicating abnormally high mutagen exposure (6.14 +/- 2.57) or genetic damage (6.94 +/- 2.48). The average respondent felt that follow-up of subjects could improve the quality of mutagen-exposure-monitoring studies (8.33 +/- 1.49), disagreed that subjects whose laboratory data suggested unusually severe exposure or damage should not be asked about possible sources of exposure (1.15 +/- 1.32), and disagreed that it was ethical to follow up but not discuss results with subjects having laboratory evidence of abnormal mutagen exposure (3.78 +/- 3.43) or genetic damage (3.06 +/- 3.17) to see how many developed cancer relative to a control group. Fifteen specific tests for measuring mutagen exposure or genetic damage were rated on a scale of 0 to 10, with 0 being "totally experimental" and 10 being "absolutely diagnostic of degree of exposure or genetic damage." Values ranged from 6.13 +/- 2.67 for karyotyping leukocytes to 3.43 +/- 2.43 for quantifying frequency of rare red cells with mutant protein. This study may help in decision making regarding follow-up of mutagen-exposed subjects.

Attitude↗
PubMed1987

Presence and measurement of sample histidine in the Ames test: quantification and possible elimination of a source of false-positive mutagenicity test results.

Both histidine and dipeptides that can be converted to histidine can potentially interfere with the Ames test by increasing the number of spontaneous revertants. Such interference might be especially evident when urine and other biological samples are studied in this assay. We have developed a turbidimetric bioassay that utilizes a nonrevertible Salmonella typhimurium histidine auxotroph, NS1135. The assay is linear with histidine over at least a 300-fold range (0.015-5 micrograms/ml of L-histidine.HCl.H2O). Data indicate that several histidine-containing dipeptides can be utilized as efficiently as free histidine. Our data suggest that this assay may be used to measure biological samples accurately for their histidine content and thereby permit an adjustment for sample histidine during the setup of Ames assays, thus eliminating increased reversion caused by sample histidine.

Biological Assay↗
PubMed1987

Effect of interferon alpha, interferon beta, and interferon gamma on the in vitro growth of human renal adenocarcinoma cells.

Interferon-alpha, interferon-beta, and interferon-gamma differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-beta was more effective than natural interferon-alpha for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-gamma. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6-10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed.

Adenocarcinoma↗
PubMed1987

Escherichia coli infection of the urinary bladder: induction of tumours in rats receiving nitrosamine precursors and augmentation of bladder carcinogenesis by N-nitrosobutyl (4-hydroxybutyl)amine.

Experimental introduction of Escherichia coli type 04 into the subserosa of the urinary bladder of female Fischer 344 rats produced chronic bacterial infection in more than 90% of animals. Groups of rats with bacterial infection were given sodium nitrate and either piperazine (Group 1) or dibutylamine (Group 2) in the drinking-water. Control, noninfected animals received nitrate and either piperazine (Group 3) or dibutylamine (Group 4). At 40 weeks, transitional-cell carcinomas of the bladder were detected in 9/30 rats in Group 1 compared to 0/34 in Group 3 (p less than 0.0005), and in 11/34 rats in Group 2 compared to 0/32 in Group 4 (p less than 0.0003). Early changes were examined by scanning and transmission electron microscopy as well as autoradiography. Preneoplastic liver foci were detected in infected groups of animals receiving amine and nitrate, indicating reabsorption of the carcinogen synthesized in situ to induce distant organ transformation. In another experiment, E. coli infection augmented bladder carcinogenesis by N-nitrosobutyl(4-hydroxybutyl)amine (NBHBA), as indicated by earlier appearance of bladder tumours (six weeks compared to nine weeks) and, after 25 weeks, higher incidences of transitional-cell carcinomas (41/46 compared to 39/53, p less than 0.05), squamous metaplasia (43% compared to 9%, p less than 0.0001), glandular metaplasia (26% compared to 13%, p less than 0.05) and muscle invasion (30% compared to 11%, p less than 0.01) in the E. coli-infected group receiving carcinogen compared to the noninfected group receiving carcinogen, respectively. These results indicate that bacterial infection of the urinary bladder may play a major role in bladder carcinogenesis, both by helping in-situ nitrosamine synthesis and by augmenting carcinogenesis by nitrosamines.

Amines↗
PubMed1986

Urine recovery experiments with quercetin and other mutagens using the Ames test.

Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz[a]anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino)-2-methoxyacridin e dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone-extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

A protocol for the combined biochemical and serological identification of the Ames mutagen tester strains as Salmonella typhimurium.

Previously published reports have noted biochemical reactions atypical of Salmonella among the Ames tester strains of Salmonella typhimurium, and an inability to assign the strains to a specific Salmonella O (heat-stable cell wall) antigen group. We studied the biochemistry and serology of strains TA97, 98, 100, 102, 104, 1535, 1537, and 1538 in an attempt to develop a protocol to correctly speciate the strains. Biochemical reactions of all eight strains using standard media supplemented with histidine and biotin were consistent with those of the genus Salmonella. Strains TA100, 104, and 1535 were assigned to Salmonella O groups using bacteria treated with hot ethanol (White schema). H (flagellar) antigen assignments were performed successfully with seven of the eight strains. Two H antigen assignments required the use of the Craigie tube test for selection of motile revertants. Combining our biochemical and serological results obtained by this protocol, we were able to correctly speciate TA100, 104, and 1535 as Salmonella typhimurium. Our results demonstrate that representatives of the tester strains can be correctly speciated provided that procedures are followed that allow for the unusual nutrient requirements, the deep rough cell wall mutation, and the variably deficient motility of these organisms.

Antigens, Bacterial↗
PubMed1986

The influence of niacin and nicotinamide on in vivo carcinogenesis.

Data concerning effects of the essential vitamin niacin and its active form nicotinamide were evaluated. Dietary deficiencies and excesses of these nutrients by themselves do not appear to exert any influence on in vivo carcinogenesis in animals. Varying results were produced when nicotinamide was administered at pharmacologic doses concurrently with or following carcinogen administration to mice or rats. Some investigators found significantly increased tumor formation, whereas others reported a decreased effect or no effect. Epidemiologic studies have not investigated the relationship between niacin deficiency or excess and carcinogenesis in humans.

Animals↗
PubMed1986

Identification of 4-(5-amino-2-furyl)thiazole (AFT) as a reductive metabolite of the carcinogen 4-(5-nitro-2-furyl)thiazole (NFT).

The chemical synthesis of 4-(5-amino-2-furyl)thiazole (AFT) and its formation during the in vitro reductive metabolism of 4-(5-nitro-2-furyl)thiazole (NFT) by rat liver tissues on anaerobic incubation with NADPH were examined. AFT was synthesized by catalytic reduction of NFT with 5% palladium on activated carbon. Purified AFT, a pale yellow powder, melted at 105 degrees C and had an extinction coefficient of 16.3 mM-1 cm-1 at 297 nm in methanol. The proton n.m.r. spectrum, i.r. and mass spectra were consistent with the assigned structure. Analysis of the ethyl acetate extract, following incubation of NFT with rat liver tissue preparations, revealed a metabolite whose chromatographic and mass spectral characteristics were the same as those obtained with synthetic AFT, thus establishing the structural identity of the metabolite as AFT. These data show that AFT is formed on reduction and could act as a precursor for the formation of 1-(4-thiazolyl)-3-cyano-1-propanone as postulated earlier.

Animals↗
PubMed1986

Mutagenicity of 3,4-diphenyl-5-nitrofuran analogs in Salmonella typhimurium.

A new series of chemicals comprising eight different 3,4-diphenyl-substituted furan analogs, namely, methyl-3,4-diphenyl-2-furoate, methyl-3,4-diphenyl-5-nitro-2-furoate, 3,4-diphenyl-5-nitro-2-furoic acid, 3,4-diphenyl-5-nitro-2-acetylfuran, 3,4-diphenyl-5-nitro-2-bromoacetylfuran, 2-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole, 2-acetyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole and 2-formyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole were synthesized and their mutagenic activities tested in Salmonella typhimurium. The structure--activity relationship studies revealed that for mutagenic activity the nitro group is essential and that the potency of activity is greatly altered by the nature of the substituent at the 2-position of the furan ring. The mutagenic activities of these chemicals were generally much higher in TA100 compared to TA98. The relative order of activities for 2-substituted, 3,4-diphenyl-5-nitrofurans were COOCH3 greater than COCH2BR greater than COCH3 greater than COOH in S. typhimurium TA100. 3,4-Diphenyl-5-nitro-2-bromoacetylfuran was equally active in nitroreductase-proficient (TA98, TA100) and in nitroreductase-deficient (TA98NR, TA100NR) strains. In contrast, the acetyl and carboxymethyl ester analogs were relatively less active in nitroreductase-deficient strains. Mutagenic activities of 3,4-diphenyl-substituted furylthiazoles in comparison with the unsubstituted analogs of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide, N-[4-(5-nitro-2-furyl)-2-thiazolyl]-acetamide and 2-amino-4-(5-nitro-2-furyl)thiazole revealed that the phenyl groups drastically reduced their mutagenic activities. However, the relative order of activities formylamino greater than or equal to acetylamino greater than amino were the were the same between phenyl-substituted and unsubstituted analogs.

Biotransformation↗
PubMed1986

Oncogenicity of hexachlorobenzene.

Subchronic and chronic toxicities of hexachlorobenzene (HCB) were studied in both sexes of Swiss mice, Syrian golden hamsters and Sprague-Dawley rats, at dietary dosages of 0, 100 and 200 ppm (mice), and 0, 200 and 400 ppm (hamsters and rats) for 90 days. At day 91, 25/50 animals in each of 18 groups were killed for histology studies. The rest were killed at 6-week intervals until the study was ended. Marked hepatosplenomegaly, enlarged thymuses and lymph nodes, or swollen and granular-looking renal cortices with depressions or nodulary areas were commonly observed. Dose- and sex-dependent progressive changes included toxic-degenerative hepatitis, chronic cirrhosis, hepatomas, bile-duct adenomas and a few hepatocarcinomas in older animals. A generalized lymphohaematopoietic response led to thymic, splenic and nodal lymphosarcomas, especially in female mice. Toxic-tubular nephritis with cortical infarcts developed into regenerative foci and renal adenomas in low incidences. Liver lesions were more prominent in females, while renal changes were most common in male rats. HCB was retested in both sexes of rats at oral doses of 0, 75 and 150 ppm for up to 2 years. At the start, each group contained 94 rats, and four randomly selected rats were killed at weeks 0, 1, 2, 3, 4, 8, 16, 32, 48 and 64 for microscopy. Progressive liver lesions started as hyperaemia and degenerations (4 weeks), and developed into toxic hepatitis, cirrhosis and formation of pre- and neoplastic foci (36 weeks), with hepatomas, bile-duct adenomas and hepatocellular carcinomas (64 weeks) in very high incidences in females and renal adenomas in male rats.

Animals↗
PubMed1986

Inhibitory effects of interferon-inducing pyrimidinones on the growth of transplantable mouse bladder tumors.

Pyrimidinones are low-molecular-weight compounds which are inducers of interferon in several animal species. They have established antiviral, immunomodulatory, and antitumor effects. Four pyrimidinones as well as another potent interferon inducer, polyriboinosinic-polyribocytidylic acid, and beta-interferon were tested for effects on growth of the transplantable mouse bladder tumor (MBT-2). The pyrimidinones 2-amino-5-bromo-6-phenyl-4(3H)pyrimidinone (ABPP) and 2-amino-5-bromo-6-(3-fluorophenyl)-4(3H)pyrimidinone (ABMFPP) significantly inhibited MBT-2 growth in a dose-dependent manner and with equal potency when injected i.p. every 4 days starting 1 day after tumor cell inoculation. Administration of ABPP p.o. was as effective as i.p. injections. Direct intravesical application of ABPP to transplantable tumors growing in the bladder may be more effective in inhibiting MBT-2 growth than the same dose introduced p.o. Although ABPP (100 mg/kg) has an inhibitory effect comparable to 5000 units of beta-interferon, both pyrimidinones even at 500 mg/kg were less inhibitory of tumor growth than 10 mg of polyriboinosinic-polyribocytidylic acid per kg. The pyrimidinones 2-amino-5-bromo-6-(2,5-difluorophenyl)pyrimidine-4(3H)one (ABDFPP) and 2-amino-5-iodo-6-(2,3-difluorophenyl)pyrimidin-4(3H)one (AIDFPP) were also of comparable potency in inhibiting MBT-2 growth and were more effective on mg/kg basis than both ABPP and ABMFPP. Treatment with ABDFPP or AIDFPP also resulted in long-term cures of up to 40% of mice. In this respect these latter two compounds were superior to treatment with 10 mg of polyriboinosinic-polyribocytidylic acid per kg, a treatment which reduced tumor size but had no effects on tumor incidence. The data suggest that tumors of bladder origin may be particularly sensitive to treatment with pyrimidinones.

Animals↗
PubMed1985

Chemical induction of ovarian tumors in rats.

The production and pathogenesis of ovarian cancer was investigated in noninbred albino weanling female rats by surgical fixation into the left ovaries of sutures chemically impregnated with the chemical carcinogens formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]hydrazide (FNT), a nitrofuran antibiotic; N-methyl-N'-nitrosourea (MNU), a direct-acting alkylating agent; or 7,12-dimethylbenz[a]anthracene (DMBA). Rats living more than 30 days following surgery were subjected to complete necropsy of external, thoracic, and abdominal tissues when they died or were killed at 407 days, the study termination. Mean survival of rats in treated and control groups was comparable. All carcinogen-treated rats exposed to FNT, MNU, or DMBA developed one or more ovarian, uterine, or mammary neoplasms with a total of 31 tumors in 22 rats as compared with no tumors in 5 control rats. All carcinogen-treated rats (22) developed ovarian adenomas (18) or adenocarcinomas (4); 3 developed uterine fibroadenomas (1) or squamous cell carcinomas (2); and 6 developed mammary adenocarcinomas. No neoplasms were present in the right ovaries of carcinogen-treated rats. These data suggest that direct application of carcinogens to ovarian tissue is a satisfactory way to develop ovarian adenoma and adenocarcinoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Serial cultivation of normal rat bladder epithelial cells in vitro.

Recent advances in culture techniques for human urothelial cells have led to the development of an improved method for growing primary rat bladder epithelial cells. We report here the conditions developed for large-scale in vitro growth and serial cultivation of normal diploid rat bladder epithelial cells. Primary cultures were initiated by attachment of bladder mucosal explants to type I collagen gels. A rapid outgrowth of epithelial cells from the explants occurred when cultured in a hormone-supplemented medium with epidermal growth factor. These primary outgrowths were passaged by nonenzymatic dispersion with 0.1 per cent ethylenediaminetetracetic acid and replating onto new gels. The capacity for routine serial passaging and maintenance of rat bladder epithelial cells required the presence of epidermal growth factor, a requirement not observed with human urothelial cells. The characteristics of the cultured rat bladder epithelial cells were similar to human urothelial cells in: ultrastructural and phase-contrast morphologic properties, showing junctional complexes, desmosomes, stratification and an apical glycocalyx; the absence of stromal cell contamination; and the ability to be serially passaged. Spontaneous cell-line formation was observed with the rat bladder epithelial cells, but has not been found with the human urothelial cells. With the method that we have developed, the number of rat bladder epithelial cells generated from a single bladder of a 4 to 6 week old rat was increased 100-fold from about 7 X 10(5) cells to 7 X 10(7) viable cells within 3 weeks of culture. The capability of culturing normal, primary rat bladder epithelial cells on this scale has not been reported previously and will facilitate comparative studies of the biological and molecular characteristics of the mammalian urothelium. Furthermore, this culture system will be useful for carcinogenesis studies, including metabolic activation of carcinogens and cellular transformation in vitro.

Animals↗