Accession Number : ADA254542
Title : Biological (Molecular and Cellular) Markers of Toxicity.
Descriptive Note : Final rept. 15 Sep 88-14 Sep 91,
Corporate Author : OAK RIDGE NATIONAL LAB TN ENVIRONMENTAL SCIENCES DIV
Personal Author(s) : Shugart, L R ; D'Surney, S J ; Gerrys-Hull, G ; Greeley, M S
Report Date : 15 Dec 1991
Pagination or Media Count : 86
Abstract : Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). A discontinuous DEN treatment inhibited the activity of a detoxication enzyme activity (ethoxyresorufin-O-deethylase) 65 percent and the activity of glutathione-S-transferase transferase 35 percent No 01-ethyl guanine adducts were detected, and a slight, but statistically significant, in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any 01-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to a similar extent in fish exposed to 25, 50, and 100 ppm DEN. This has been observed also in medaka exposed to BaP. Flow cytometric analysis of DEN exposed liver tissue showed that cell killing and stimulation of replacement cell production occurred during exposure. An increased rate of cell division and fixation of DEN induced mutation may be an important early component of liver carcinogenesis. Following a series of exposures to BaP (I ug/L), there was an increase in fecundity and in the number of ovarian vitellogenic oocytes. Japanese Kodak and; Chemical carcinogensis; DNA damage; Diethylnitrosamine; Benzo(a)pyrene; Detoxification; Developmental abnormalities; RA3.
Descriptors : *POLYACRYLAMIDES , *GENETICS , *ABNORMALITIES , *TRANSFERASES , *ONCOGENESIS , *HISTONES , *DETOXIFICATION , MEASUREMENT , DAMAGE , CHEMICALS , WATER , CELLS , ENZYMES , HEAT , GUANINE , CHROMATIN , GLUTATHIONE , ALKALINITY , EXCISION , FISHES , ELECTROPHORESIS , NUMBERS , LIVER , DEOXYRIBONUCLEIC ACIDS , MUTATIONS , REPLACEMENT , MARKERS , CELL DIVISION
Subject Categories : Biochemistry
Distribution Statement : APPROVED FOR PUBLIC RELEASE