Enhancing effects of captafol on the development of GST-P-positive liver cell foci in a medium-term bioassay, and protection by L-cysteine of the enhancement in rats.
The modifying effects of captafol and protective effects of L-cysteine on the development of glutathione S-transferase placental form-positive (GST-P +) foci of the liver and expression of proliferating cell nuclear antigen (PCNA) in the kidney were investigated in a medium-term bioassay using D-galactosamine (DGA) in rats. Male 6-week-old F344 rats were initially given a single i.p. injection (200 mg/kg) of diethylnitrosamine (DEN) and after 2 weeks on basal diet, received two i.p. injections of DGA (300 mg/kg) at the ends of weeks 2 and 5, and were fed a diet supplemented with test chemicals for weeks 3-8. Animals in group 1 were given 1500 ppm captafol in the diet, while group 2 received 1500 ppm captafol in diet as well as 1500 ppm L-cysteine in drinking water, animals in control group being given basal diet alone. Positive results regarding increased numbers and areas of GST-P + liver cell foci were obtained in rats treated with captafol alone. On the other hand, significant reduction by L-cysteine in the areas of GST-P + liver cell foci initiated by DEN and promoted by captafol was observed. In addition, the PCNA-labelling indices of renal tubule cells were elevated in rats treated with captafol alone and significantly reduced in rats treated simultaneously with L-cysteine. The protocol used in the present study therefore allowed the in vivo determination of promoting effects of captafol and inhibitory influence of L-cysteine by analyzing GST-P + foci in the livers as marker lesions, within a relatively short period of 8 weeks. Thus, this bioassay protocol could have applicability as a new in vivo assay system for the screening of hepatic carcinogenic or anti-carcinogenic agents.
Kim
H C
HC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Jangdong, Yusong-ku, Daejon, South Korea.
Cha
S W
SW
Song
S W
SW
Ha
C S
CS
Han
S S
SS
Roh
J K
JK
Lee
Y S
YS
Furukawa
F
F
Nishikawa
A
A
Takahashi
M
M
D000818:Animals; D002215:Captan / Q000031:analogs & derivatives* / Q000633:toxicity; D015197:Carcinogenicity Tests; D053138:Cyclohexenes; D003545:Cysteine / Q000494:pharmacology*; D005659:Fungicides, Industrial / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D053138:Cyclohexenes; D005659:Fungicides, Industrial; D018809:Proliferating Cell Nuclear Antigen; C001614:captafol; D005982:Glutathione Transferase; D002215:Captan; D003545:Cysteine