Alachlor,
metolachlor, and
propachlor are widely used chloroacetanilide
herbicides. Their cytotoxicity in rat (Fa32) and human (Hep G2)
hepatoma-derived cells was investigated, in connection with their influence on the endogenous
glutathione (GSH) content, on the
xenobiotic-metabolizing phase I
enzymes 7-ethoxyresorufin O-deethylase (
EROD) and 7-pentoxyresorufin O-depentylase (
PROD), and phase II
glutathione transferase (GST). The cytotoxicity was measured by the
neutral red uptake inhibition assay. The following toxicity range was observed in both cell lines:
propachlor >
alachlor >
metolachlor. When the endogenous GSH content was reduced by pretreatment of the cells with L-
buthionine (S,R)-sulfoximine, the cytotoxicity of the
herbicides increased strongly in both cell lines.
EROD and
PROD activities were dose-dependently increased to different degrees in Fa32, as was
EROD in Hep G2, but no
PROD activity was observed in these cells. The GSH content was not altered after 1 h treatment, and was approximately doubled after 24 h. GST activity was increased in Fa32 cells but not in Hep G2. A comparable cytotoxicity was observed for the investigated chloroacetanilides in both the rat and the human cell lines. Different interactions with
xenobiotic-metabolizing phase I and II
enzymes were observed, and GSH showed a protective effect against the
acetanilides in both cell lines.