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 (0.05 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 x 10(8) 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.
Kawai
K
K
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611-3008, USA.
Kawamata
H
H
Kameyama
S
S
Rademaker
A
A
Oyasu
R
R
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008770:Methylnitrosourea / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology
D004815:Epidermal Growth Factor; D008770:Methylnitrosourea