Bioactivation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene by sulfation in the rat liver changes during the cell cycle.
Sulfation activity towards N-hydroxy-2-acetylaminofluorene and 4-nitrophenol was determined in male rat liver cytosol at several time points after partial hepatectomy corresponding to G1-, S-, and M-phase. N-hydroxy-2-acetylaminofluorene sulfation activity decreased by 80% when hepatocytes entered the G1-phase. This lower activity was maintained during the S-phase and M-phase, but was restored when hepatocytes entered the G0-phase again. Sulfation activity towards 4-nitrophenol did not alter after hepatectomy. Various other cytosolic enzyme activities were determined after hepatectomy to investigate the specificity of the decrease in sulfation activity. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased in the S- and M-phase by maximally 80% and 60%, respectively. Glutathione-S-transferase and glutamate-pyruvate transaminase activity did not alter during the cell cycle. These results indicate that sulfation of N-hydroxy-2-acetylaminofluorene in hepatocytes may depend on the phase of the cell cycle. The relevance of the finding is discussed in relation to the resistance of proliferating (pre)neoplastic hepatocytes to the toxic and mitoinhibitory effects of N-hydroxy-2-acetylaminofluorene.
Gilissen
R A
RA
Division of Toxicology, Leiden University, The Netherlands.
Meerman
J H
JH
D000818:Animals; D001711:Biotransformation; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000201:enzymology; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D009596:Nitrophenols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015238:Sulfotransferases / Q000378:metabolism*
D009596:Nitrophenols; D006881:Hydroxyacetylaminofluorene; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D015238:Sulfotransferases; C024836:4-nitrophenol