Intraluminal Epidermal Growth Factor Affects Growth of N‐Methyl‐N‐nitrosourea‐initiated Rat Bladder Carcinoma

To confirm our recent finding that epidermal growth factor (EGF) appeared to contribute to the tumor‐enhancing effect demonstrated by normal rat urine, we conducted 2 experiments using our heterotopically transplanted rat urinary bladder model. In experiment 1, after a single dose (0.25 mg) of N‐methyl‐N‐nitrosourea (MNU), we intravesically administered EGF (0.5 ml of 500 ng/ml phosphate‐buffered saline) once a week for 30 weeks. Instillation of EGF induced a significantly larger number of tumors than did instillation of the vehicle (P=0.03). EGF without MNU initiation did not induce tumors. In experiment 2, 2 groups received instillation of killed Escherichia coli (5 × 10⁸ cells)/0.5 ml phosphate‐buffered saline once a week for 4 weeks to expand the MNU‐initiated cell population. Subsequent EGF treatment significantly increased the incidence of tumors (P=0.01). In the groups which did not receive killed E. coli, EGF treatment induced a significantly higher number of tumors than did vehicle treatment (P<0.001). All of the tumors were low‐grade, superficial transitional cell carcinomas. These observations indicate that EGF acts as a growth‐stimulating factor on dormant neoplastic cells and thereby increases the number of tumors.