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Carcinogenesis, Vol. 20, No. 7, 1247-1252, July 1999
© 1999 Oxford University Press

Carcinogenesis

Elevation of urinary enzyme levels in rat bladder carcinogenesis

Emile M. Youssef1, Hideki Wanibuchi, Satoru Mori, Elsayed I. Salim, Shuji Hayashi and Shoji Fukushima2

First Department of Pathology, Osaka City University Medical School,1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan

Urinary enzyme levels were investigated in rats administered different promoters in their diet for 32 weeks after being initiated by treatment with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks. All groups were composed of 10 rats each. Group 1: females treated with 3% uracil (100% carcinoma incidence). Group 2: control females kept on basal diet only (0% carcinoma incidence). Group 3: males treated with 5% sodium L-ascorbate (100% carcinoma incidence). Group 4: control males (0% carcinoma incidence). Urine was collected at the end of weeks 12, 24 and 36 and tested for lactate dehydrogenase (LDH), alkaline phosphatase, N-acetyl-ß-D-glucosaminase and aspartate aminotransferase activity. To facilitate comparison, data were related to the corresponding excreted creatinine levels. All measurements were made using a centrifugal automatic analyzer. The urine of rats with cancer lesions (groups 1 and 3) showed significant elevation in all enzyme activities at weeks 24 and/or 36 except for LDH in females (group 1). The M/H ratio of the LDH isozymes was reversed (1.10 ± 0.10) in the tested rats with carcinomas at week 36. This study thus provides evidence of a correlation between high urinary enzyme levels and cancer development in the rat bladder. Measurement of the tested enzymes might thus provide a method to detect malignant changes in bladder epithelium by direct urine analysis.

Abbreviations: AAT, aspartate aminotransferase; ALP, alkaline phosphatase; BBN, N-butyl-N-(4-hydroxybutyl)nitrosamine; HE, hematoxylin and eosin; LDH, lactate dehydrogenase; Na-AsA, sodium L-ascorbate; NAG, N-acetyl-ß-D-glucosaminase; PN, papillary or nodular.

1 Present address: Department of Molecular Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan

2 To whom correspondence should be addressed Email fukuchan{at}med.osaka-cu.ac.jp


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