In vitro exposure of human uroepithelial cells to occupational chemical results in alterations in protein expression as determined by high resolution two dimensional polyacrylamide gel electrophoresis.
Kanitz-MH; Savage-RE; Athota-K; Reznikoff-C; Swaminathan-S; Frederickson-S
Toxicologist 1995 Mar; 15(1):201-202
A study has been initiated to investigate the carcinogenicity of 4,4-methylene bis(2-chloroaniline)(MOCA) and 2-phenyl-l,4-benzoquinone (PBQ) and to identify biomarkers of effects of exposure to these workplace-associated suspect carcinogens. High resolution two dimensional polyacrylamide gel electrophoresis (2D PAGE) was used to examine changes in protein expression in chemically-treated human uroepithelial cells (HUC). Previously, HUC has been shown to be sensitive to malignant transformation by 4-aminobiphenyl (4-ABP) and its metabolites (Bookland, et., at, Cancer Research, 52;160&1614, 1992). HUC was incubated for 24hr with the controls, dimethylsulfoxide (DMSO)or N-OH-AABP as well as N-OH-MOCA(2.5 and .10 uM), or PBQ (1.5.and 3.5 uM) which resulted in 25% and 75% cell kill, respectively. A 2D PAGE protein map of treated HUC was developed using the ISO-DALT method of Anderson. Electrophoretic pattern comparison across treatment groups by scanning densitometer and computer analysis revealed quantitative changes in a specific subset of proteins in the 10 uM MOCA-treated HUC and N-OH-AABP-treated HUC but not the DMSO-treated HUC. Preliminary studies of tumor incidence in athymic mice suggest that neo-plastic transformation occurred only in the 10 uM MOCA-treated HUC. These results show that occupational chemical exposure of HUC results in 2D PAGE protein alterations which may be useful for the identification of biomarkers associated with bladder tumorigenesis.
Exposure-assessment; Exposure-limits; Animal-studies; Laboratory-animals; Occupational-exposure; Carcinogens; Tumorigenesis; Bladder-cancer; Bladder-disorders; Endocrine-system-disorders
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland