This study was carried out to establish the non-surgical medium-term carcinogenicity bioassay model using D-galactosamine(DGA) in the rats. Eighteen. Chemical compounds were tested in this study(chlordane diethystilbestrol.
a-hexaclorocyclohexane,
urethane, benzo [a]pyrene, carbazole, dimethylnitrosamine, orotic acid, sodium nitrate, bytylated hydroxyanisole, clofibrate, di(2-thylhexyl)phtalate.. diaminodiphenylmethane, sodium saccharin, 8-introquinoline, quercetin, dimethylsulfoxide and
8-metholquinoline).
A total of 168-week-old male Fischer rats were divided into 18 test groups and 3 control groups. All the test and control rats were given a single intraperitoneal dose of diethylnitrosamine(200mg/kg body weight) on the initiation day of the
experiment,
and these rats were also given D-galactosamine(300mg/kg body weight) intraperitoneally at 2 and 5 weeks of the experiment. The rats in one of the 18 test groups were given one of the 18 test chemical compounds through the diet for 6 weeks, and
the
rats
in control groups were given corn oil through the diet for 6 weeks. Every rat in both groups was sacrificed at 8 weeks and liver tissues were taken for histopathological and immunohistochemical examinations.
@ES The results obtained were as follows:
@EN The numbers and areas of GST-p positive foci in the livers of test rats dosed with chlordane, diethylstilbestrol, -hexaclorocyclohexane, urethane, benzo[a]pyrene, dimethylnitrosamine, orotic acid, diaminodiphenylmethane, sodium saccharin
and
dimethylsulfoxide, respectively were significantly increased in comparing with those of control group. The mean numbers of silver binding nucleolar organizer regions (AgNORs) per nucleus of hepatic cells in test rats dosed with chlordane, DES and
-HCH,
respectively significanly increased comparing with those of control groups. There was no positive result in all test groups when GST-p positive foci in the liver and the mean number of AgNORs per nucleus of the hepatic cells were used as markers
for
preneoplastic lesions. A detection rate of hepart sarcinogens obtained by measuring the GST-p positive foci was 89% and that of non-liver carcinogens was 33%. The detection rate of hepatocarcinogens obtsined by measuring the mean nubers of AgNORs
per
nucleus of hepatic cells was 33%.
The results indicate that measuring the GST-p positive foci in the livers of rats after dosing with the chemical compounds is reliable for carcinogenicity bioassay. But it seems that the measurment of the numbers of AgNORs in the hepatic cell
nucleus is
not so useful in the rats for this study model.
|