Biomaterial Database

The kinetics of DNA alkylation, repair and replication in hepatocytes, Kupffer cells, and sinusoidal endothelial cells in rat liver during continuous exposure to 1,2-dimethylhydrazine. 1983

J G Lewis, and J A Swenberg

We have previously shown that when rats are continually exposed to 1,2-dimethylhydrazine (SDMH) in a manner that induces malignant hemangioendotheliomas of the liver there was both accumulation of promutagenic DNA damage, as measured by O6-methylguanine (O6MG) and a selective increase in cell replication in the target cell population, the nonparenchymal cells (NPC). Hepatocytes rapidly repaired O6MG and had only modest increases in cell replication. In this study, we have further separated the NPC into Kupffer cells (KC) and sinusoidal endothelial cells (SEC) and have determined the kinetics of O6MG and 7-methylguanine (7MG) formation and repair, and cell replication in each individual cell type. O6MG concentrations were highest over the entire exposure period in the SEC, lowest in the hepatocytes, with intermediate concentrations occurring in KC. 7MG concentrations were lower in SEC than in KC or hepatocytes resulting in greatly increased O6/7MG ratios in SEC suggesting a lower capacity for SDMH metabolism and O6MG repair. Moreover, the concentrations of 7MG and the pattern of accumulation were sufficiently similar in KC and hepatocytes to suggest similar capacities of these two cell types to activate SDMH. Rates of cell replication were greatly elevated in both KC and SEC by SDMH, while hepatocyte replication was barely affected. These data suggest that SEC and to a lesser extent KC have greater potential for initiation due to mispairing of O6MG than do hepatocytes. The data further suggest that alkylation in SEC may arise from metabolites generated by neighboring hepatocytes or KC.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007728	Kupffer Cells	Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood and dispose of worn out red blood cells.	Kupffer Cell,Cell, Kupffer,Cells, Kupffer
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008763	Methylhydrazines	Hydrazines substituted by one or more methyl groups in any position.
D008855	Microscopy, Electron, Scanning	Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY.	Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D008858	Microscopy, Phase-Contrast	A form of interference microscopy in which variations of the refracting index in the object are converted into variations of intensity in the image. This is achieved by the action of a phase plate.	Phase-Contrast Microscopy,Microscopies, Phase-Contrast,Microscopy, Phase Contrast,Phase Contrast Microscopy,Phase-Contrast Microscopies
D010587	Phagocytosis	The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).	Phagocytoses
D002265	Carboxylic Ester Hydrolases	Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.	Carboxylesterases,Ester Hydrolases, Carboxylic,Hydrolases, Carboxylic Ester
D004127	Dimethylhydrazines	Hydrazines substituted with two methyl groups in any position.	Dimethylhydrazine