Hirofumi Matsuda

Effect of Methimazole on Rat Renal Carcinogenesis Induced by N-Ethyl-N-Hydroxyethylnitrosamine

The effect of methimazole on N- ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal lesions was investigated in a medium-term initiation/promotion bioassay in male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ), alone or in combination with methimazole, to the diet for 20 wk. The addition of methimazole reduced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors that arose in EHEN + NTA groups. Methimazole also decreased the bromodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of α 2u-globulin in treated kidneys as compared to controls. It appears that methimazole exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against renal damage but not against tumorigenesis, probably arising from genotoxic insult.

GENETIC VARIATIONS IN HUMAN BENIGN PROSTATIC HYPERPLASIA DETECTED BY RESTRICTION LANDMARK GENOMIC SCANNING

Alterations in the genomic DNAs of benign prostatic hyperplasias were examined using restriction landmark genomic scanning. This methodology allows the visual comparison of a large number of loci as spots within a gel that has been electrophoresed in 2 dimensions. Within each of the 16 hyperplasias examined, we found 2 to 10 spots with altered intensities, as compared to equivalent spots from normal prostate, but could detect few common spot profiles for any hyperplasia samples. These data conflict with data from previous studies and suggest that there may be no consistent genetic changes in the pathogenesis of some forms of human benign prostatic hyperplasia.

Different Expression of nm23-H1 and nm23-H2 Protein with Proliferative Activities in Various Sizes of Human Renal Cell Carcinoma

Ninety-five paraffin blocks of renal cell carcinomas (RCCs) and background normal tissue were obtained from patients in Nara Medical University Hospital and used for studying silver-binding nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA) and nm23 oncogenes. The RCCs were grouped by size (< or = 30, > 30 and < or = 50, > 50 mm of average diameter) and grade according to the General Rules for Clinical and Pathological Studies of Renal Cell Carcinoma, Japan. Numbers of cases were 17 in the < or = 30-mm group, 36 in the > 30- and < or = 50-mm group, and 42 in the > 50-mm group. AgNOR scores were 4.68 +/- 1.22, 3.91 +/- 1.31 and 3.01 +/- 1.05, respectively, with significant intergroup differences. Frequencies of PCNA-positive cells per 500 cells were 33.8 +/- 23.5, 39.4 +/- 13.8 and 45.9 +/- 38.8. nm23-H1 immunohistochemical staining proved strongly positive in 21 of 24 areas of normal proximal convoluted tubules, 4 of 8 dysplasia cases, 2 of 17 in the < or = 30-mm group RCCs, 1 of 36 in the > 30- and < or = 50-mm group RCCs and none of 42 in the > 50-mm RCCs. nm23-H2 in contrast was weakly positive in 3/24, 2/8, 12/17, 30/36 and 20/42 of the cases, respectively. The results indicated an inverse relationship between tumor size and score of AgNOR without any variation in PCNA labeling and contrasting expression of nm23-H1 and nm23-H2 linked to the size of RCCs.