Epoprostenol sodium, a prostaglandin I2, lacks tumor promoting effects in a medium-term liver carcinogenesis bioassay in rats.
Potential modifying effects of epoprostenol sodium administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats daily received subcutaneously epoprostenol sodium at doses of 0, 1, 10 and 100 microg/kg, or were fed phenobarbital sodium (PB) at a dietary level of 500 parts per million (ppm) as positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. Prominent flushing of extremis and signs of behavioural depression occurred after injection and lasted for 1 h in rats given 100 microg/kg epoprostenol sodium. Such clinical signs were slight in rats treated with 10 microg/kg, but not observed with 1 microg/kg. Marked decrease in body weight gain was noted in rats given 100 microg/kg. Statistically significant changes in relative liver weights were not found in any group given the test chemical. Epoprostenol sodium did not significantly increase the quantitative values for glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive control. The results thus demonstrate that epoprostenol sodium lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.
Kawabe
M
M
Daiyu-Kai Institute of Medical Science, 64 Goura, Nishiazai, Azai-cho, 491-0113, Inchinomiya, Japan.
Hagiwara
A
A
Yoshino
H
H
Miyashita
K
K
Nakanishi
T
T
Sano
M
M
Tamano
S
S
Okamoto
K
K
Miura
K
K
Tokado
H
H
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D011464:Epoprostenol / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D000959:Antihypertensive Agents; D011464:Epoprostenol; D005982:Glutathione Transferase