Subject(s)
Benzopyrenes/metabolism , Bronchi/metabolism , DNA/metabolism , Trachea/metabolism , Urinary Bladder/metabolism , Animals , Benzo(a)pyrene , Cells, Cultured , Chromatography, High Pressure Liquid , Cricetinae , Dogs , Humans , Macaca mulatta , Male , Mesocricetus , Rats , Species SpecificitySubject(s)
Aflatoxins/metabolism , Bronchi/metabolism , Carcinogens/metabolism , DNA/metabolism , Trachea/metabolism , Urinary Bladder/metabolism , Aflatoxin B1 , Animals , Binding Sites , Biotransformation , Cells, Cultured , Chromatography, High Pressure Liquid , Cricetinae , Dogs , Haplorhini , Humans , Liver/metabolism , Rats , Rats, Inbred F344ABSTRACT
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.
Subject(s)
Benzopyrenes/metabolism , Bronchi/metabolism , DNA/metabolism , Urinary Bladder/metabolism , Adolescent , Adult , Aged , Benzo(a)pyrene , Benzopyrenes/pharmacology , Bronchi/drug effects , Child , Chromatography, High Pressure Liquid , Colon/metabolism , Esophagus/metabolism , Female , Humans , Male , Middle Aged , Organ Culture Techniques , Smoke , Smoking , Time Factors , Trachea/metabolism , Urinary Bladder/drug effectsSubject(s)
Adult , Child , Dinoprostone , Female , Humans , Male , Prostaglandins E/urine , Radioimmunoassay/methods , Semen , TritiumABSTRACT
The effect of salt-loading on urinary prostaglandin D2 (PGE2) was studied in the rat. PGE2 doubled after 4 days of gavage with 40 ml 0.9% saline. Control animals receiving 5% glucose or tap water did not show this increase. When rats were allowed ad lib saline, PGE2 increased after 2 weeks, but returned to normal at 5 weeks. This same phenomenon of increased PGE2 early in the course of salt-loading was also observed in Dahl salt-sensitive and salt-resistant rats fed an 8% salt diet. Inhibition of prostaglandin biosynthesis by meclofenamate or indomethacin did not attenuate the natriuretic effect of saline loading. We conclude: 1) Salt-related changes in PGE2 is a time-dependent phenomenon, and 2) PGE2 is not the natriuretic factor since levels normalize despite continued salt-loading, and natriuresis was unaffected by prostaglandin blockade.
