We will study the intracellular distribution of chromium and the mechanisms of chromium toxicity in mammalian cells. With Cr(VI), increased SCE frequency occurred at 0.01 micromolar, whereas the inhibition of cell proliferation occurred at 1.0 micromolar. Cr(III) was much less effective. Our working hypothesis is that the genotoxic effects of Cr(VI) are causually related to the antiproliferative effects. We will study the transport of 51-Cr (VI and III) into cells and of their distribution in intracellular organelles. We expect that chromium toxicity is associated with changes in chromatin conformation (DNA superstructure). Our plan is to: study cytogenetic changes by chromium by using assays which measure chromatid aberrations, chromosomal aberrations and SCE; utilize computer-aided cell sizing equipment to detect small changes in cell growth and cell size; develop chromium- resistent and chromium - transformed cells; use a variety of analyses to monitor alterations in these cell variants; study the effects of chromium on the uptake of nucleotide precursors and cellular nucleotide pools; use the following preparations for biochemical studies: intact cells, permeabilized cells, nucleoids and isolated chromosomes; study the effects of chromium on the fidelity of DNA synthesis, and on the conformation of chromatin in these preparations.

Agency
National Institute of Health (NIH)
Institute
National Institute for Occupational Safety and Health (NIOSH)
Type
Research Project (R01)
Project #
5R01OH001630-04
Application #
3420165
Study Section
Safety and Occupational Health Study Section (SOH)
Project Start
1983-09-30
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Kansas
Department
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160
Garrison, J C; Bisel, T U; Peterson, P et al. (1990) Changes in hepatocyte ploidy in response to chromium, analyzed by computer-assisted microscopy. Fundam Appl Toxicol 14:346-55
Garrison, J C; Peterson, P; Uyeki, E M (1989) Computer-based image analysis of cartilage differentiation in embryonic limb bud micromass cultures. J Microsc 156:353-61
Garrison, J C; Uyeki, E M (1988) The effects of gamma radiation on chondrogenic development in vitro. Radiat Res 116:356-63
Garrison, J C; Pettit, G R; Uyeki, E M (1987) Effect of phorbol and bryostatin I on chondrogenic expression of chick limb bud, in vitro. Life Sci 41:2055-61
Nakanishi, S; Uyeki, E M (1985) Benzamide on chondrocytic differentiation in chick limb bud cell culture. J Embryol Exp Morphol 85:163-75