AJP - Cell Physiology, Vol 262, Issue 1 C122-C127, Copyright © 1992 by American Physiological Society
Buthionine sulfoximine-induced cytostasis does not correlate with glutathione depletion
Y. J. Kang and M. D. Enger
Department of Zoology and Genetics, Iowa State University, Ames 50011.
The effects of L-buthionine-(S,R)-sulfoximine (BSO) on the proliferation of
normal rat kidney fibroblasts (NRK-49F) were determined and compared with
the effects of BSO on cellular glutathione (GSH) content. The proliferation
rate of exponentially growing NRK-49F cells was found to be slowed in 0.01
and 0.1 mM BSO and arrested in 1.0 and 10 mM BSO. There is no retardation
in the proliferation of cells cultured in 0.001 mM BSO. However, varying
BSO concentrations at and above 0.1 mM did not result in concordant
differences in the rate and extent of GSH depletion. A dose-dependent
effect of BSO on GSH levels was observed at BSO concentrations less than or
equal to 0.01 mM. BSO was found also to inhibit epidermal growth factor
(EGF)-induced DNA synthesis in NRK-49F cells arrested by serum deprivation
in a dose-dependent pattern dissimilar to that of BSO-induced cellular GSH
depletion. Removal of BSO allowed cells to resume proliferation. Further,
growth-arresting BSO treatments were found to affect neither cell viability
nor colony-forming efficiency. Addition of exogenous GSH or cysteine
overcame BSO inhibition of EGF-induced DNA synthesis but not BSO depletion
of cellular GSH levels. BSO was further found to inhibit the uptake of
cysteine, cystine, and alpha-[1-14C]-methylaminoisobutyric acid (MeAIB) by
the EGF-stimulated quiescent cells in a dose-dependent fashion. The results
presented here thus demonstrate that BSO inhibits the proliferation of
NRK-49F cells. This effect, however, does not correlate with BSO-induced
cellular GSH depletion and is not due to an overt toxic effect.(ABSTRACT
TRUNCATED AT 250 WORDS)
