The objective of the proposed investigation is to demonstrate the urinary factor(s) responsible for induction of transitional epithelial tumors by a chemical carcinogen. As a working model, an isograft bladder transplanted on the back of male inbred ACI/Cox rats will be used. The incidence of bladder tumors observed after repeated instillations of bladder carcinogen dibutylnitrosoamine derivatives (N-butyl-N-(3-carboxypropyl) nitrosoamine (BCPN) and N-butyl-N-(4-hydroxybutyl) nitrosoamine (BBN)) dissolved in water and injected into the isograft lumens will be compared with that of bladder tumors observed after the administration of the carcinogen plus urine dialysate (UD) or urea, a major organic component of urine. Once urea and/or UD has demonstrated a tumor-enhancing effect, the UD will be fractionated by appropriate procedure to various fractions and each fraction will be tested by the same technique. All the above described work will be conducted in parallel to the similar in vitro study which aims at isolation of the growth-promoting and/or carcinogen-enhancing factors responsible for in vivo and in vitro growth.