Characterization of Cytochrome P450-Dependent and Glutathione Transferase Activities in SV 40-Immortalized Uroepithelial Cell Lines: Possible Role in Transformation and Tumor Formation

Details

• Personal Author:
  Frederickson SM ; Reznikoff CA ; Savage RE Jr. ; Snawder, John E. ; Swaminathan S
• Description:
  An in vitro/in vivo transformation system has been developed as a model for bladder tumorigenesis. SV40-immortalized human uroepithelial cells are exposed to putative carcinogens and then implanted into athymic nude mice to testfortumorigenesis. Studies with 4-aminobiphenyl(4-ABP) demonstrated that one cell line, SV-HUC-PC, was sensitive to chemical-induced transformation and another line, SV-HUC-BC, was refractory. We are currently testing this system as a model to identify occupational carcinogens and develop biomarkers of exposure and effects of exposure. As part of this study, we examined P450- dependent metabolism, glutathione transferase, and the effects of chemicals on deoxyribonucleic acid(DNA)synthesis and repair in SV-HUC-PC and SV-HUCBC. Activities for CYP1A1/1A2, CYP3A, and CYP2B1/2B2 were estimated by determining o-dealkylation of ethoxy-, benzoxy-, and pentoxy-resorufin, respectively. Coumarin hydroxylase and p-nitrophenol hydroxylase were used to estimate CYP2A and CYP2E1, respectively. SV-HUC-PC microsomes had five fold greater CYP1A1/1A2 activity and two fold higher CYP3A activity than SV-HUCBC. CYP2B1/2B2 and CYP2A activities and glutathione transferase were not different between the two cell lines. DNA synthesis and repair, by BrdU incorporation, was not different between the two lines when N-methyl-N-nitroN-nitrosoguanidine (MNNG) or other reactive metabolites were tested; however, SV-HUC-PC was more sensitive to n -nitrosodimethylamine, 4-ABP, and 4,4-methylene bis (2-chloroaniline) (MOCA). The data demonstrate that, while these cells have retained form-specific P450 activities, SV-HUC-PC has greater CYP1A1/1A2 and CYP3A activities. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Carcinogens Laboratories Neoplasms Occupational Health Safety Urogenital Diseases Urogenital System
• Keywords:
  Animal-studies Author Keywords: Glutathione Transferase Bladder-cancer Bladder-disease Bladder-disorders Cell-transformation Exposure-levels In-vitro-studies In-vivo-studies Laboratory-animals Models Tumorigenesis Tumors

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• ISSN:
  1051-7235
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Ohio ; OSHA Region 5 ; Wisconsin
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DART - Division of Applied Research and Technology
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  195-201
• Volume:
  10
• Issue:
  3
• NIOSHTIC Number:
  nn:20025219
• Citation:
  Toxicol Methods 2000 Jul; 10(3):195-201
• Contact Point Address:
  John E. Snawder, NIOSH, Taft Laboratories, MS-C23, 4676 Columbia Parkway, Cincinnati, OH 45226, USA
• CAS Registry Number:
  4-Aminobiphenyl (CAS RN 92-67-1) ; Coumarin (CAS RN 91-64-5)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology Methods
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:9b73fb17866da8b23f86ea4772f392aadd2293d726b61f3277709d171a302575ff1b481e21e03e8cf945987cfedfe19e28f196fcb4004a3310752ab538e59f97
• Download URL:
  https://stacks.cdc.gov/view/cdc/196688/cdc_196688_DS1.pdf
• File Type:
  [PDF - 143.54 KB ]