Experimental evidence suggests that rat urine plays a dual role in urinary bladder carcinogenesis, as a carrier of carcinogen(s) and an enhancer (or promoter) of carcinogenesis in carcinogen-initiated cells. The present experiment was conducted to determine whether tumor-enhancing activity exhibited by the whole urine resides in a specific fraction(s) when separated by molecular weight. Normal rat urine after preliminary filtration to remove gross debris was filtered through Amicon Diaflo membranes to obtain two types of filtrate, one at an exclusion level of M.W. 1,000 and the second at an exclusion level of M.W. 50,000. These filtrates were tested for tumor-enhancing activity in the heterotopically transplanted rat urinary bladders (HTBs) removed from rats pretreated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine in drinking water for 4 or 10 weeks. The incidences of cancer in HTBs receiving repeated instillations of the filtrate at M.W. 50,000 did not differ significantly from those of the HTBs receiving whole urine but were significantly higher than those of the HTBs receiving the filtrate at M.W. 1,000. In the HTBs, which had been exposed to the carcinogen for a longer period of time (10 weeks), the filtrate at M.W. 1000, enhanced the bladder tumorigenesis over that of the osmolality control. The results indicate that there may be two classes of tumor-enhancing activity: the first and major one being in the fraction above M.W. 1000; and a second one being below M.W. 1000. The latter fraction appears to exert its effects only on the cells which are in an advanced stage of carcinogenesis.


Supported by USPHS Grant CA 14649 through the National Bladder Cancer Project, Northwestern University Medical School. Department of Pathology Funds, and in part by Cancer Center Core Grant CA 15145.

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