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Biomedical subjects

G N Wogan

Publications and source records attributed to G N Wogan.

At least 163 records · Page 9Linked to original sources
PubMed1968

Mycotoxins.

Explore the source record for details and available documents.

Aflatoxins↗
PubMed1966

Aflatoxin B1: binding to DNA in vitro and alteration of RNA metabolism in vivo.

Aflatoxin B(1) binds to both native and denatured DNA, as shown by spectroscopy and equilibrium dialysis. It also strongly inhibits incorporation of cytidine into rat liver nuclear RNA and lowers the RNA content of the nucleus. The extremle toxicity and carcinogenicity of aflatoxin B(1) may be direct results of the affinity of this agent for DNA.

Aflatoxins↗
PubMedDate not supplied

Peracylation of nucleosides with methionine: foundation for a method to detect carcinogen adducts.

We report the chemical foundation for a new method to detect carcinogen-DNA adducts, which we have designated adduct detection by acylation with methionine (ADAM). The method is based on reaction of DNA adducts with a protected methionine derivative, (tert-butoxycarbonyl)-L-methionine N-hydroxysuccinimidyl ester (TMB-NHS). Acylation of 2'-deoxyguanosine (dGuo), used as a prototypical deoxynucleoside, and N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dGuo-8-ABP), the major DNA adduct formed after in vivo exposure to 4-aminobiphenyl, a known human carcinogen, with TBM-NHS was optimized, and products were characterized by 3H radioactivity, UV absorbance, mass spectrometry, and 1H and 13C NMR. Derivatives acylated on hydroxyl (5' or 3') and/or amine (N2) groups were unambiguously determined to be mono-, bis-, and tris-TBM-acylated nucleosides. Under optimal acylation conditions [TBM-NHS (> or = 4 x 10(5) molar equivalents), pyridine (50 microL), THF (50 microL), and diisopropylcarbodiimide (DIC) (1 microL) and incubation for 2 h at 37 degrees C], the efficiency of acylation for picomole or smaller quantities of dGuo-8-ABP exceeded 95%, with the tris-TMB-acylated nucleoside representing the major product (88%). A linear correlation was obtained between the amount of [3H]dGuo-8-ABP introduced into the reaction and the total amount of TBM-acylated products formed. These results support the validity of this strategy for adaptation as an analytical method for the detection of low levels of DNA adducts through the use of (tert-butoxycarbonyl)-L-[35S]-methionine N-hydroxysuccinimidyl ester.

Acylation↗
PubMedDate not supplied

Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa.

Hepatocellular carcinoma is one of the major human cancers, causing at least 250,000 deaths each year. Two of the major risk factors for this disease are aflatoxin exposure and hepatitis B virus. This study was undertaken to explore the relationship between dietary exposure to aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people who were either hepatitis B virus surface antigen-positive or -negative. The diets of 20 individuals, 10 males and 10 females, with ages ranging from 15 to 56 years, were monitored for 1 week, and aflatoxin intake levels were determined for each day. Starting on the fourth day, total 24-h urines were consecutively obtained for 4 days. The subjects were generally paired for hepatitis B virus status. Preparative monoclonal antibody affinity chromatography/high-performance liquid chromatography and competitive enzyme-linked immunosorbent assays were carried out on each of the urine samples, and the relationship between aflatoxin intake values and the excretion of (a) total aflatoxin metabolites and (b) aflatoxin-N7-guanine (AFB-N7-guanine) was determined. The average intake of total aflatoxins was 12.0 micrograms for the entire study group during the 1-week collection period. However, there was considerable day-to-day variation in exposures, from a low of zero to a high of 29.6 micrograms total aflatoxins/day. Initial efforts to characterize total aflatoxin metabolites in the urine samples were made by competitive enzyme-linked immunosorbent assay. The correlation coefficient for the analysis was 0.65, with P < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Dietary intake of aflatoxins and the level of albumin-bound aflatoxin in peripheral blood in The Gambia, West Africa.

Aflatoxin is implicated as a risk factor for hepatocellular carcinoma in areas of the world with a high incidence of this tumor. The present study was designed to validate the use of aflatoxin-albumin adducts in peripheral blood as a measure of individual exposure to this carcinogen. Dietary intake of aflatoxin was measured at the individual level in 20 residents of Keneba, West Kiang, The Gambia, over a 7-day period and correlated with the level of aflatoxin bound to peripheral blood albumin at the beginning and end of the study. Complementary enzyme-linked immunosorbent assay and high-performance liquid chromatography-fluorescence techniques were used to assay the aflatoxin adducts. All subjects were exposed to aflatoxin originating from several food types, with an average daily intake of 1.4 micrograms/day. A significant correlation (r = 0.55; P = < 0.05) was observed between the dietary intake and the level of albumin-bound aflatoxin at the end of the study. In addition, a good agreement was obtained with the two analytical techniques. A comparison of matched chronic hepatitis B surface antigen carriers with noncarriers did not reveal any difference in adduct formation for a given dietary intake of aflatoxin. These studies demonstrate the validity of aflatoxin-albumin adducts as a marker of human exposure to this carcinogen.

Adolescent↗
PubMedDate not supplied

Mutagenicity and antibacterial activity of mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum.

Twelve mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum in solid-state fermentation on grains were purified and tested for mutagenicity and antibacterial activity in Salmonella/mammalian microsome assays. The mutations studied were reversions of histidine auxotrophs to prototrophy in strains TA98 and TA100 and forward mutations to 8-azaguanine resistance (8AGR) in strain TM677. Rubroskyrin, (+)rugulosin, lumiluteoskyrin [a photoproduct of (-)luteoskyrin], and simatoxin [a new water-soluble metabolite of unknown structure] induced 8AGR mutations in strain TM677 but not histidine reversions in strains TA98 and TA100. Mutagenic potency was reduced by rat-liver microsomes. The carcinogens (-)luteoskyrin and cyclochlorotine were antibacterial but not mutagenic. (+)Rugulosin, rubroskyrin, lumiluteoskyrin, and high concentrations of simotoxin were also antibacterial. Antibacterial activity but not mutagenicity was observed with pibasterol and skyrin. Chrysophanol, islandicin, iridoskyrin, and emodin were inactive as mutagens or as antibacterial agents.

Animals↗