The inhibitory effects of pentamidine on biochemical events in human liver cells.
The present study was undertaken to determine the biochemical effects of pentamidine on an established human liver cell line (HEP-G2) and its drug resistant subclone (HEP-G2DR). The HEP-G2DR cells were included in the study in order to determine whether drug resistance played a role in any of the observed effects seen during and/or following pentamidine treatment. The results indicate that a 5 mum concentration of the drug significantly reduced the level of protein synthesis, as well as the continued expression of albumin, a tissue-specific product of both cell lines. Pentamidine also significantly inhibited DNA synthesis in HEP-G2 cells, but not in HEP-G2DR cells, during the first 24 hr. Conversely, only the resistant cells showed a significant recovery in both protein and albumin synthesis after the drug was removed (reversal). The significant recovery in these biochemical parameters was observed during the initial 24-hr reversal period, while a recovery in albumin secretion was not obtained in the HEP-G2 cells even after 72 hr. There was no apparent stimulation in the activity of various phase II drug metabolizing enzymes following pentamidine treatment. These findings suggest that resistance plays a role in the mechanism of action of pentamidine, since biochemical modulation of both cell lines is brought about by the drug, but only the resistant cells appear to recover fully following the removal of pentamidine from the culture medium.
Parker
C L
CL
Department of Anatomy, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Finley
R B
RB
Wright
B G
BG
Nzeribe
R
R
Stewart
J
J