Effect of retinoic acid on cell proliferation kinetics and retinoic acid receptor expression of colorectal mucosa.

Abstract

To investigate the effect of retinoic acid (RA) on cell proliferation kinetics and retinoic acid receptor (RAR) expression of colorectal mucosa. One hundred sixty healthy male Wistar rats were randomly divided into 4 groups. Rats in groups I and II were subcutaneously injected with dimethylhydrazine (DMH) (20 mg/kg, once a week,) for 7 to 13 weeks, while groups III and IV were injected with normal saline. Rats in groups II and III were also treated with RA (50 mg/kg, every day, orally) from 7th to 15th week, thus group IV was used as a control. The rats were killed in different batches. The expressions of proliferating cell nuclear antigen (PCNA), nucleolar organizer region-associated protein (AgNOR) and RAR were detected. The incidence of colorectal carcinoma was different between groups I (100 %) and II (15 %) (P<0.01). The PCNA indices and mean AgNOR count in group II were significantly lower than those in group I (F=5.418 and 4.243, P<0.01). The PCNA indices and mean AgNOR count in groups I and II were significantly higher than those in the groups III and IV (in which carcinogen was not used) (F=5.927 and 4.348, P<0.01). There was a tendency in group I that the longer the induction with DMH the higher PCNA index and AgNOR count expressed (F=7.634 and 6.826, P<0.05). However, there was no such tendency in groups II, III and IV (F=1.662 and 1.984, P>0.05). The levels of RAR in normal and cancerous tissues in groups treated with RA were significantly higher than those in groups not treated with RA (F=6.343 and 6.024, P<0.05). RA decreases the incidence of colorectal carcinoma induced by DMH. Colorectal cancer tissue is associated with abnormal expression of PCNA, AgNOR and RAR. RA inhibits the expression of PCNA and AgNOR, and increases RAR concentration in colorectal tissues.