Reappraisal of eight representative carcinogenic and non-carcinogenic compounds in a new medium-term rat liver bioassay using D-galactosamine.
The carcinogenic potential of eight different compounds was assayed in a new medium-term carcinogenicity bioassay using D-galactosamine (DGA) as a non-surgical method to induce regeneration in place of partial hepatectomy (PH). Male 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 end of weeks 2 and 5. They were treated with one of the test compounds aflatoxin B1, benzo[a]pyrene, diethylstilbestrol, urethane, sodium saccharin, bucetin, D-mannitol and sodium chloride in the diet or basal diet alone for weeks 3-8. Carcinogenic potential was assessed by comparing the numbers and areas per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the livers of treated animals with those of the control animals given DEN/DGA alone. Positive estimations of carcinogenicity were obtained for the hepatocarcinogens aflatoxin B1, diethylstilbestrol or urethane, and for the non-liver carcinogen benzo[a]pyrene. Negative values were shown in rats treated with the non-carcinogens, D-mannitol and sodium chloride. The two other non-liver carcinogens sodium saccharin and bucetin, also did not exert positive effects in the system. The present data are consistent with findings in previous medium-term bioassays using PH. Our results thus confirm that the present bioassay protocol with repeated administration of DGA instead of PH may offer a new and sensitive non-invasive method to screen large numbers of environmental carcinogens.
Kim
H C
HC
Toxicology Research Center, Korea Research Institute of Chemical Technology, Daejon, South Korea.
Cha
S W
SW
Ha
C S
CS
Roh
J K
JK
Lee
Y S
YS
Furukawa
F
F
Nishikawa
A
A
Takahashi
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests / Q000379:methods*; D002273:Carcinogens / Q000633:toxicity*; D005688:Galactosamine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results
D002273:Carcinogens; D005688:Galactosamine; D005982:Glutathione Transferase