Antitumoral effect of recombinant mistletoe lectin on chemically induced urinary bladder carcinogenesis in a rat model

BACKGROUND. The objective of this study was to determine the effect of intr avesically applied, recombinant, galactoside specific mistletoe lectin (rML ) on chemically induced tumor development in the urinary bladder of rats. METHODS. For tumor induction, rats were treated with four biweekly 1.5 mg d oses of N-methyl-N-nitrosourea (NMU) intravesically (Weeks 0, 2, 4, and 6). The control group (n = 39 + 17 rats) received no other treatment. The four therapy groups also received rML twice weekly according to one of the foll owing instillation regimens: 1) 30 ng rML per instillation from Week 8 to W eek 13 (Group a: n = 14 rats), 2) 150 ng rML per instillation from Week 8 t o Week 13 (Group b: n = 23 + 15 rats), 3) 30 ng rML per instillation from W eek 14 to Week 19 (Group c: n = 22 rats), and 4) 150 ng rML per instillatio n from Week 14 to Week 19 (Group d: n = 19 rats). After the rats were asphy xiated at Week 21, the urinary bladders were excised in tote and examined h istopathologically. To study the immunomodulatory effects of intra vesicall y applied rML, 17 animals from the control group and 15 animals from Group b were asphyxiated at Week 13, and urinary bladder tissue was analyzed by s emiquantitative reverse transcriptase-polymerase chain reaction analysis fo r mRNA expression of interferon-gamma, interleukin-10, and Fas ligand. RESULTS, By Week 21, atypical hyperplasia and neoplastic transformation wer e found in 82% of the animals in the control group. In contrast, in all fou r cohorts that were treated with rML, significantly lower rates of atypical hyperplasia and neoplastic transformation were found (Group a, 50%; Group b, 52%: Group c, 45%; and Group d, 42%). By Week 13, in the bladder tissue of 15 rML-treated animals from Group b, lower expression of interleukin-10 mRNA was measured, whereas the expression levels of interferon-gamma mRNA a nd Fas ligand mRNA were comparable to those of 17 animals from the control group. CONCLUSIONS. The current data provide evidence for an inhibitory effect of rML on experimental urothelial carcinogenesis that does not seem to be due to interferon-gamma and/or interleukin-10 dependent mechanisms. (C) 2001 Am erican Cancer Society.