Expression of cytokines, TNF-alpha and IL-1 alpha, in MAM acetate and 1-hydroxyanthraquinone-induced colon carcinogenesis of rats.

The expression of cytokines, TNF-alpha and IL-1 alpha, was examined by means of a reverse transcription followed by PCR (RT-PCR) in rat colon carcinogenesis. Forty male F344 rats were used and divided into four groups. At the start of the experiment, 20 rats were treated with methylazoxymethanol (MAM) acetate (25 mg/kg body wt, one time, i.p.) and divided into two groups; group 1 was exposed to 1% 1-hydroxyanthraquinone (1-HAQ) and group 2 was fed a basal diet during the experiment (40 weeks). Other rats were also divided into two groups; group 3 was exposed to 1% 1-HAQ as group 1, and group 4 was used as control. Tumor incidence (100%) and multiplicity (5.00 +/- 2.05) in group 1 were significantly greater than those in group 2 (20% and 0.2 +/- 0.42) and group 3 (10% and 0.10 +/- 0.32) (P < 0.01 and P < 0.01 respectively). RT-PCR technique with RNA was applied to the tissues from colon neoplasms and mucosa in each group. Expression of TNF-alpha and IL-1 alpha in the colon neoplasms was much stronger than that in the colon mucosa of each group (P < 0.001 and P < 0.01 respectively). The expression of TNF-alpha was more remarkable in the colon mucosa of group 1 than that in corresponding tissue of groups 2 and 3 (P < 0.01). The expressions of TNF-alpha and IL-1 alpha were more increased in the colon mucosa of groups 1, 2 and 3 than that in group 4 as control (P < 0.01 and P < 0.05 respectively). The results indicate that TNF-alpha and IL-1 alpha may act as growth factors in rat colon carcinogenesis by MAM acetate and 1-HAQ. In addition, the synergistic effect of 1-HAQ with MAM acetate in colon carcinogenesis might be related to biological effects of the cytokines expressed in the inflammatory condition generated by 1-HAQ.