To study the effect of natural killer (NK) activity on chemical carcinogenesis in urinary bladder cancer, beige mice (NK difficient mice) and C57BL/6 mice (NK normal mice) received N-bytyl-(4-hydroxybutyl) nitrosamine (BBN) in drinking-water. The effect was evaluated by measuring the incidence of early neoplastic change in the urinary bladder. OK-432, a biological response modifier, was administrated in drinking-water and its effect on carcinogenesis was evaluated.
The beige and C57BL/6 mice were divided into two groups. Group A, C57BL/6 mice and group C, beige mice received 0.1% BBN in their drinking-water. Group B, C57BL/6 mice, and group D, beige mice, received 0.1% BBN and OK-432 (5KE/1000ml) in their drinking-water for 4 weeks. The mice were sacrificed at 12, 14, 16, 18 and 24 weeks after BBN administration and the urinary bladder was examined histologically by light and scanning electron microscopy.
In the light microscopic findings, all groups had no neoplastic change at 12, 14 and 16 weeks, although at 18 and 24 weeks, neoplastic changes were observed. The incidence at 18 weeks was 0/10 in group A, 0/8 in group B, 2/5 in group C and 3/9 in group D and that at 24 weeks was 1/8 in group A, 1/9 in group B, 2/5 in group C and 3/6 in group D. (p<0.01 between beige and C57/BL/6 mice at 18 weeks).
In the scanning electron microscopic findings, cells with a cobble stone appearance, pleomorphic microvilli and short uniform microvilli on luminal surfaces are observed during cacinogenesis in urinary bladder. Their incidence was 2/10 in group A, 1/11 in group B, 5/6 in group C and 4/5 in group D at 16 weeks, 2/10 in group A, 0/8 in group B, 7/10 in group C and 7/9 in group D at 18 weeks and 0/8 in group A, 0/9 in group B, 4/6 in group C and 3/6 in group D at 24 weeks. (p<0.01, between beige and C57BL/6 mice at 16, 18 and 24 weeks).
In conclusion, urinary bladder carcinogenesis induced by BBN neoplastic lesion was observed earlier in beige mice lacking NK activity than in C57BL/6 mice.
These results suggest an important role of NK activity in immune surveillance of chemical carcinogenesis in the urinary bladder.
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