Significant experimental decrease
of the hepatocarcinoma incidence
in C3H/Sy mice after long-term administration
of EB1089, a vitamin D analogue
D. Sahpazidou, P. Stravoravdi, T. Toliou
Theagenio Cancer Hospital, Thessaloniki, Hellas EB1089, a
Vitamin D analogue without the acute side effects of the original
vitamin, exerts strong antiproliferative activities in malignant
cells, including hepatoma cells in vitro and in experimental hepatomas
in animals as well. It also induces cell cycle arrest and apoptosis
in premalignant conditions, suggesting its application in chemopreventive
trials. We examined the possible chemopreventive effect of EB1089
on hepatocellular carcinoma incidence in C3H/Sy virgin female
mice, a strain developing an incidence of 58% spontaneous hepatomas.
A total of 95 mice, 16 weeks old, were used. EB1089 injections
of 0.5 ėg/kg of body weight were given intraperitoneally every
other day for 2, 4 and 6 months to 51 mice (18,19 and 14 mice
respectively). The rest 44 mice were divided into 3 control groups,
accordingly, and injected with the vehicle solution only. The
mice were sacrificed when they appeared moribund because of their
disease. The rest were sacrificed at the age of at least 84 weeks.
A full autopsy was performed and liver tissue was processed for
histological examination. The results obtained show that only
3.9% of treated mice developed hepatocellular carcinomas, exclusively
in the 2 month group, compared to 36.4% of hepatocellular carcinomas
in the control group. Our results suggest that the chemopreventive
administration of EB1089 causes a very statistically significant
(p<0.0001) inhibitory effect on hepatocellular carcinoma incidence
of C3H/Sy mice. This effect could be usuful in a potential application
of the chemopreventive control of hepatocarcinomas.
Key words: Experimental study, Spontaneous tumors, Chemoprevention.
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