Search PubMed⌕ Search

Biomedical subjects

F B Daniel

Publications and source records attributed to F B Daniel.

At least 73 records · Page 4Linked to original sources
PubMed1982

Metabolism and DNA binding of benzo[a]pyrene in cultured human bladder and bronchus.

The metabolism of benzo[a]pyrene (BP) was examined in explant cultures of human bladder and bronchus. Three-day cultures were exposed to radiolabeled BP for 24 h, and the metabolism was determined by analysis of the level of binding of reactive metabolites to DNA, and by the release of metabolites into the medium. For a given individual, the DNA binding level and extent of metabolism was usually higher in the bladder than in the bronchus. In specimens obtained from 16 individuals, the average DNA-binding levels for BP-DNA adducts following a 24 h exposure to 1 microM BP were 6.4 +/- 5.0 mumol BP/mol deoxyribonucleotide for the bladder and 3.1 +/- 1.9 mumol BP/mol deoxyribonucleotide for the bronchus. The major BP-DNA adduct in both tissues co-chromatographed with one of the adducts formed by reaction of r-7, t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene with deoxyguanosine using high-pressure liquid chromatography. In tissues obtained from the same individual, the binding levels of BP metabolites to bladder cell DNA was not strongly correlated to that of bronchial cell DNA (r = 0.55). The medium of both tissues contained small amounts of free, unconjugated metabolites of BP (less than 3% of the total) and large amounts (30-86% of the total) of unidentified, highly polar material. Human bladder appears to be the most active explant tissue yet studied with respect to its ability to activate BP to DNA binding forms. The relevance of this observation to human bladder cancer is, as yet, unknown.

Adolescent↗
PubMed1982

7, 12-dimethylbenz [a] anthracene-deoxyribonucleoside adduct formation in vivo: evidence for the formation and binding of a mono-hydroxymethyl-DMBA metabolite to rat liver DNA.

The polycyclic aromatic hydrocarbon, 7,12-dimethyl benz[a] anthracene (DMBA) is a potent carcinogen to the female Sprague-Dawley rat, and when administered under conditions that have been shown to produce cancer, resulted in extensive formation of hydrocarbon-deoxyribonucleoside adducts. Sephadex LH-20 and reverse-phase h.p.l.c. and spectrofluorometric analysis of these adducts demonstrate that at least one adducts results from the binding of 7, 12-dimethylbenz [a] anthracene-1,2,3,4-tetrahydro-3,4,-dihydroxy-1,2,-oxide. In these experiments, employing i.p. administration of the hydrocarbon, a second more polar adduct was observed. Evidence is presented that this adduct results from the formation of a monohydroxymethyl-methyl-benz [a] anthracene-A-ring-diol-epoxide. While both of the monohydroxymethyl-DMBA metabolites have been shown to bind cellular DNA following their administration this is the first evidence of monohydroxymethyl-DMBA-deoxyribonucleoside adducts being formed after the administration of DMBA per se. The evidence suggests that this more polar adduct is a 7-hydroxymethyl-12-methylbenz[a]anthracene-deoxyribonucleoside adduct.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Tumor-initiating activity of 4-fluoro-7,12-dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice.

We have determined the skin tumor-initiating activity in SENCAR mice of two A-ring derivatives of 7,12-dimethylbenz[a]anthracene (DMBA). 4-Fluoro-7,12-dimethylbenz[a]anthracene at a dose of 200 nmol per mouse exhibited weak activity, producing 0.6 papillopmas per mouse; doses of 10 and 20 nmol per mouse had no activity. A derivative of DMBA with the A-ring reduced, 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene (1,2,3,4,-H-DMBA), had substantial tumor-initiating activity when compared with the parent hydrocarbon. In one experiment, doses of 10 and 100 nmol per mouse gave rise to 1.6 and 9.5 papillomas per mouse, respectively; similar results were obtained in 3 additional experiments. Although the tumor-initiating activity of 1,2,3,4,-H4-DMBA was approximately one-tenth that of DMBA, this derivative was slightly (17%) more active than benzo[a]pyrene. 1,2,3,4-H4-DMBA was tested for the ability to induce mutations to 6-thioguanine-resistance in Chinese hamster V79 cells. In the absence of feeder cells capable of metabolizing polycyclic hydrocarbons, it was not mutagenic. However, in a cell-mediated mutation assay with secondary hamster embryo cells as activators, this derivative produced mutations in a dose-dependent manner and was approximately one-tenth as active as DMBA. These results indicate that metabolism of DMBA at positions 1-, 3-, 2- and 4- is important for biological activity and that for certain derivatives (i.e., 1,2,3,4-H4-DMBA), alternate pathways of metabolic activation may also be important.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1980

Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts.

Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the mechanism of action of this economically important class of carcinogenic compounds known as mineral fibers and particulates. While the length and diameter of various forms of asbestos have been associated with both cellular toxicity in vitro and tumor occurrence in vivo, nothing is known about whether or not these same physical properties are responsible for the purported synergistic interaction between cigarette smoking and asbestos exposure relative to the induction of bronchogenic carcinoma. Thus, while the risk of bronchogenic carcinoma for nonsmokers exposed to asbestos appears to be only slightly greater than that for unexposed nonsmoking populations, the risk of occurrence of this same tumor in asbestos workers who also smoke is approximately 100-fold greater than in nonsmoking asbestos workers. The risk of bronchogenic carcinoma is increased approximately 8-fold in asbestos workers who smoke over non-exposed smokers. Since it is clear that cigarette smoke contains over 150 polycyclic aromatic hydrocarbons, some of which are known animal carcinogens, and since other laboratories have reported that metals associated with asbestos redirect the metabolism of these agents, it was of interest to us to investigate the effects of mineral fibers on the metabolism and biochemistry of polycyclic aromatic hydrocarbons.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Mass spectral characterization of the K-region and non K-region dihydrodiols of 7,12-dimethylbenz (a) anthracene.

Dihydrodiols are derived from intermediary arene oxides during the metabolism of polycyclic aromatic hydrocarbons. In this study, the mass spectra of the trimethylsilyl ether derivatives obtained from the 5,6-dihydrodiol and 8,9-dihydrodiol of 7,12-dimethylbenz [a] anthracene were compared. The mass spectral fragmentation patterns indicate some key features in distinguishing a K-region dihydrodiol from its non K-region isomer. The 8,9-dihydrodiol, a non K-region metabolite, exhibits a greater tendency to undergo a ring contraction fragmentation process while the K-region 5,6-dihydrodiol participates preferably in other fragmentation pathways. The data presented in this report will be useful in charcterizing K-region and nonK-region metabolic epoxidation of polycyclic aromatic hydrocarbons.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

DNA repair in Syrian hamster embryo cells treated with 7,12-dimethylbenz[a]anthracene and its weakly carcinogenic 5-fluoro analog.

The postreplication repair capacity of Syrian hamster embryo cells in culture was determined after treatment with the potent carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) and its weakly carcinogenic analog 5-F-DMBA. The size and amount of daughter DNA sedimenting as high-molecular-weight DNA were found to be less in the DMBA treated cells than in the 5-F-DMBA-treated cells. This difference probably depends upon the types of adducts entering DNA replication.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Comparative metabolism and DNA binding of 7,12-dimethylbenz[a]anthracene and its weakly carcinogenic 5-fluoro analog.

Cultured Syrian hamster embryo cells readily convert both the carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA), and its weakly carcinogenic analogue, 5-fluoro-7,12-dimethylbenz[a]anthracene (5F-DMBA), to water soluble metabolites. DMBA, however, binds to the hamster cell DNA at least 2.8-3.0 times more extensively than 5F-DMBA. Likewise, 5F-DMBA is converted to water soluble metabolites by liver microsomal preparations at a rate equal to DMBA, but the latter compound binds to DNA 2.6-3.2 times more effectively.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1976

Osmium (VI) complexes of the 3', 5'-dinucleoside monophosphates, ApU and UpA.

The dinucleoside monophosphates, ApU and UpA, react with potassium osmate (VI) and 2,2'-bipyridyl to form the corresponding oxo-osmium (VI) bipyridyl sugar ester in which the osmate group is bonded to the terminal 2',3'-glycol. Osmium (VIII) tetroxide and 2,2'-bipyridyl react with the dinucleosides to form the corresponding oxo-osmium (VI) bipyridyl heterocyclic esters which result from addition of the tetroxide to the 5,6-double bond of the uracil residue. Although capable of transesterification reactions, these heterocyclic esters are exceptionally stable toward exchange reactions in solution. No apparent exchange was observed after 1 month. This reaction thus seems promising for single-site osmium labeling in polynucleotides.

Adenine Nucleotides↗
PubMedDate not supplied

Fourteen-day toxicity study of 1,3,5-trinitrobenzene in Fischer 344 rats.

Toxic effects of 1,3,5-trinitrobenzene (TNB) in male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of TNB (0, 50, 200, 400, 800 and 1200 mg kg-1 diet) for 14 days. Food intake by female rats in 400, 800 and 1200 mg TNB diet groups was reduced and resulted in a significant decrease in absolute body weights (BW). Food and water consumption by male rats in high-dose groups (800 and 1200 mg TNB kg-1 diet) was also reduced and resulted in a significant decrease in body weight. The calculated average TNB intake (from 1200 mg TNB kg-1 diet) was 92 mg kg-1 BW day-1 for male rats and 80 mg kg-1 BW day-1 for females. A decrease in testicular weight in males and an increase in spleen weight of both sexes in high-dose groups was noted. In addition, histopathological examinations revealed that the susceptible organs for TNB toxicity were kidney (hyaline droplets), spleen (extramedullary hematopoiesis), brain (hemorrhage, malacia and gliosis) and testes (seminiferous tubular degeneration). Hematology and clinical chemistry studies indicated a decrease in red blood cell count and hematocrit, a decrease in alkaline phosphatase, an increase in Heinz bodies and increased methemoglobin concentration as compared to controls in both sexes. A lowest observed adverse effect level of 4.41 mg TNB kg-1 BW day-1 was established based on the findings of this study.

Anemia↗
PubMedDate not supplied

Carcinogenic evaluation of 2,3-dimethyl-2,3-dinitrobutane via the mouse skin bioassay.

Female SENCAR mice initiated with 2,3-dimethyl-2,3-dinitrobutane (DMDNB) and promoted with 12-O-tetradecanoylphorol-13-acetate (TPA) via the SENCAR mouse skin bioassay did not exhibit a significant increase in skin tumors. The mice received 20 mg kg-1 DMDNB divided into six intragastric doses over 2 weeks and were promoted three times per week for 20 weeks.

Animals↗
PubMedDate not supplied

Chronic toxicity of 1,3,5-trinitrobenzene in Fischer 344 rats.

The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60, and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23, 2.68, 13.31 mg/kg body weight (BW)/day respectively. Terminal body weights were decreased and water intake was increased in both sexes (300 ppm), whereas food consumption was decreased in males (60 and 300 ppm groups) only. The relative spleen weights were significantly decreased in both sexes (300 ppm), whereas the relative brain weights were increased in females only (300 ppm). Hematological effects were not observed in animals killed at the 2-year time point, except significant decrease in the mean corpuscular hemoglobin (MCH) in males (300 ppm) and in females (60 and 300 ppm). Methemoglobin levels were increased in both sexes in the high dose group. Histopathological examination showed treatment-related changes in the kidney (hyaline droplets; 60 and 300 ppm) and the spleen (erythroid cell hyperplasia and pigment deposition; 300 ppm) of both sexes. Cytoplasmic hyaline droplets in the kidneys were characterized by immunohistochemistry as alpha-2mu-globulin. We propose a chronic, oral no-observable-adverse-effect level (NOAEL) of 2.68 mg/kg BW/day for TNB in the rat, based on the hematological and renal changes.

Administration, Oral↗