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Biomedical subjects

A Czech

Publications and source records attributed to A Czech.

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

Metabolism and mutagenic activity of benzo[k]fluoranthene and 3-, 8- and 9-fluorobenzo[k]fluoranthene.

The metabolism of 3-, 8- and 9-fluorobenzo[k]fluoranthene (B[k]F) relative to B[k]F was investigated. The major metabolites of B[k]F formed in vitro using rat liver S-9 metabolism systems were 8,9-dihydro-8,9-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 3-, 8- and 9-hydroxyB[k]F. Fluorine substitution within the structure of B[k]F substantially altered the types of metabolites formed in vitro. The most pronounced effect was observed with 9-fluoroB[k]F. In contrast to B[k]F, the 8,9-dihydro-8,9-dihydroxy-, 9-hydroxy- and 10,11-dihydro-10,11-dihydroxy derivatives were not detected as metabolites of 9-fluoroB[k]F. However, either the 2,3- or 4,5-dihydrodiol of 9-fluoroB[k]F was detected. In the case of 8-fluoroB[k]F, neither the 8- nor 11-hydroxy- derivatives were detected. The principle dihydrodiols formed from 8-fluoroB[k]F were the 10,11-dihydrodiol and either the 2,3-or 4,5-dihydrodiol. The pattern of metabolites formed with 3-fluoroB[k]F was similar to that observed with B[k]F with the exception that neither the 3- nor 4-hydroxy derivatives were formed. Mass spectral data indicated that fluoro substitution is not lost to any appreciable extent during the metabolism of 3-, 8- and 9-fluoroB[k]F. The mutagenic activity of these B[k]F fluoro derivatives along with B[k]F, 2,3-dihydro-2,3-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 8,9-dihydro-8,9-dihydroxyB[k]F were evaluated in Salmonella typhimurium TA100 in the presence of rat liver S-9 metabolism systems. 3-FluoroB[k]F was more mutagenic than B[k]F, while both 8- and 9-fluoroB[k]F were less active. While the 2,3-dihydrodiol and 2,3-quinone were weakly active, the 8,9-dihydrodiol had similar mutagenic potency to B[k]F.

Animals↗
PubMed1987

Tumorigenic activity of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) and N'-nitrosonornicotine (NNN) on topical application to Sencar mice.

The tumor-initiating activities of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) and N'-nitrosonornicotine (NNN) were evaluated on the skin of female SENCAR mice. A total initiator dose of 28 mumol/mouse of each nitrosamine was applied in 10 subdoses administered every second day. Promotion commenced 10 days after the last initiator dose and consisted of twice weekly application of 2.0 micrograms of tetradecanoylphorbol acetate for 20 weeks. NNK induced a 79% incidence of skin tumors with an average of 1.6 tumors/mouse and a 59% incidence of lung adenomas. In contrast, iso-NNAL and NNN were not active as tumor initiators in either the skin or lung of mice. The tumorigenic activity of NNK on SENCAR mouse skin was evaluated at several doses. At a total initiator dose of 28 and 5.6 mumol/mouse, NNK exhibited significant activity (P less than 0.005) inducing a 59% and 24% incidence of skin tumors, respectively. In this dose response bioassay, NNK at a total initiator dose of 28 mumol induced a 63% incidence (P less than 0.005) of lung adenomas. The numbers of lung adenomas induced at the lower doses employed were not significant. NNK, at a total initiation dose of 1.4 mumol, did not exhibit significant tumorigenic activity (P greater than 0.05). Analysis of DNA from the skin of mice treated with NNK using HPLC with fluorescence detection failed to detect O6- and N-methylguanine (O6-MG and N7-MG) adducts. These data indicate that NNK can exert a contact carcinogenic effect and suggest that mechanisms other than DNA methylation may be involved in its activation to a tumorigenic agent in mouse skin.

Administration, Topical↗
PubMed1983

Glycosylated hemoglobin (Hb AI) as an indicator of therapy effects in different clinical types of diabetes.

The levels of glycosylated hemoglobin (Hb AI), intermittent glycemia and glycosuria over 24 hr, Mw index, fasting serum cholesterol and triglycerides, and 24-hr proteinuria were determined in 20 healthy subjects and 88 diabetics representing different clinical types of diabetes mellitus. In each of the subjects all the tests were carried out on a single day. The other investigations included endogenous creatinine clearance, ECG and ophthalmoscopic examination of the eye-fundus. The mean Hb AI levels in the "A" control group (up to 40 yr of age) and in the "B" control group (41-60 yr) were mean +/- SD = 6.8 +/- 0.65% and mean +/- SD = 6.49 +/- 0.99% of the total hemoglobin concentration, respectively. A significant increase in Hb AI concentration was found in all the diabetic patients. The increase, independent of the subject's age, clinical type of diabetes and the therapy employed, was related to the degree of hyperglycemia. In Type I diabetes there was no positive correlation between Hb AI concentration on the one hand and fasting glycemia, the 24-hr profile of glycemia, glycosuria and Mw index on the other. The latter indices of diabetes mellitus control seem thus to differ in value and significance. In Type II diabetes, both newly-diagnosed and of long duration, treated with the sulfonylurea derivatives, a marked correlation was found between Hb AI level and fasting glycemia, the mean value of 8 glycemia determinations over 24-hr, Mw index and 24-hr glycosuria. In Type II diabetes treated with insulin a correlation was established between Hb AI and other findings, except fasting glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗