膀胱腫瘍のリスク要因としての膀胱炎に関する実験的研究 : N-butyl-N-(4-hydrokybutyl) nitrosamine (BBN)誘発ラット膀胱発癌に及ぼす炎症の影響
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Administrations of 0.01% and 0.005% BBN were undertaken in female Sprague Dawley rats (aged 12 weeks) and female Wistar rats (aged 16 weeks) for 4 and 8 weeks, respectively. Escherichia coli isolated from the urine of patients with urinary tract infections, which invade the rat tunica mucosa vesicae urinariae to varying degrees, were transurethrally inoculated into the bladder.When 0.1ml of 103/ml bacteria of a highly invasive strain was inoculated twice at intervals of 2 weeks before, during and after the administration of 0.01% BBN, the incidences of tumors were 64.3% (9/14), 57.1% (8/14) and 46.7% (7/15), respectively. Administration of BBN alone resulted in a tumor incidence of 33.3% (5/15). Transitional cell carcinoma was observed in only two animals in which inflammation was induced after BBN administration.Among the animals given 0.005% BBN after the induction of inflammation, 69.2% (9/13) of those inoculated twice with 0.1ml of 103/ml bacteria of the highly invasive strain at intervals of 4 weeks had tumors (papilloma in one and hyperplasia in eight). The incidence of tumors in animals which had the combined treatment was lower than the 77.8% (14/18) found in the animals which received only a single administration of BBN (hyperplasia in 14), but the tumors were larger in the latter group. The incidence was highest in animals inoculated four times with 0.1ml of 105/ml bacteria of a moderately invasive strain at intervals of three weeks, 87.6% (14/16). Half of them had transitional cell carcinoma or squamous cell carcinoma. There were significant differences (p<0.01) in both the number of tumors occurring in one animal and the sizes of the tumors in the single administration group and the combined treatment group. In contrast, the incidence was lowest, 43.8% (7/16), in animals inoculated four times with 0.1ml of 108/ml bacteria of a moderately invasive strain at intervals of three weeks. All the animals with tumors showed simple hyperplasia of less than 1mm in diameter, indicating a decrease in carcinogenesis.From these results, it was concluded that tissues with inflammatory changes are more likely to be initiated by a carcinogenic substance than are normal tissues, in so far as the inflammatory changes induce no separation or destruction of basal cells even if superficial cells are separated. When inflammatory changes occurred in the tissues during the promotive stage, the inflammation stimuli also exerted a promoting effect on tumor formation.
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