PMID- 23885864 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130729 LR - 20130726 IS - 1354-750X (Print) IS - 1354-750X (Linking) VI - 4 IP - 3 DP - 1999 TI - Induction of cytochrome P450 1A and DNA damage in isolated rainbow trout (Oncorhynchus mykiss) hepatocytes by 2,3,7,8 tetrachlorodibenzo-p-dioxin. PG - 214-28 LID - 10.1080/135475099230886 [doi] AB - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatocytes isolated from immature rainbow trout (Oncorhynchus mykiss) by collagenase perfusion were investigated with respect to induction of cytochrome P450 1A (CYP1A) enzyme activities and protein contents as well as DNA damage. Exposure of primary rainbow trout hepatocytes to TCDD resulted in increased CYP1A contents, as determined by immunoblotting, enhanced activities of 7-ethoxyresorufin-O-deethylase (EROD) and increased DNA damage as determined by the comet assay. By means of electron microscopy, no symptoms of cytotoxicity could be observed except for slight increases of lysosomal components and the smooth endoplasmic reticulum. Whereas CYP1A contents constantly increased over the duration of the entire experiment, EROD activities remained constant from day 3 of exposure to 1 nM TCDD; maximum induction of CYP1A activities was reached with 0.1 nM TCDD after 5 days. DNA damage increased in a time- and dose-dependent fashion until day 3. After 5 days, DNA damage was less pronounced, and the number of damaged nuclei declined in all TCDD concentrations. Since TCDD has been shown to not directly react with DNA, metabolism of TCDD or TCDD-induced changes in other metabolic pathways are suspected to result in the production of DNA-reactive (endogenous) substances. FAU - T Berbner N Rahman T Braunbeck AU - T Berbner N Rahman T Braunbeck LA - eng PT - Journal Article PL - England TA - Biomarkers JT - Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals JID - 9606000 EDAT- 1999/01/01 00:00 MHDA- 1999/01/01 00:01 CRDT- 2013/07/27 06:00 PHST- 2013/07/27 06:00 [entrez] PHST- 1999/01/01 00:00 [pubmed] PHST- 1999/01/01 00:01 [medline] AID - 10.1080/135475099230886 [doi] PST - ppublish SO - Biomarkers. 1999;4(3):214-28. doi: 10.1080/135475099230886.