Biomedical subjects

Shugo Suzuki

Publications and source records attributed to Shugo Suzuki.

24 records · Page 2Linked to original sources

PubMed2003

Age-dependent histopathological findings in the prostate of probasin/SV40 T antigen transgenic rats: lack of influence of carcinogen or testosterone treatment.

Sequential changes in the phenotype of prostatic lesions and the impact of additional carcinogen treatment or castration on development and progression of prostate cancers were examined in probasin/simian virus 40 (SV40) T antigen transgenic (TG) rats. Non-invasive prostate adenocarcinomas were evident in all lobes at 15 weeks of age. Invasive tumors were limited to the anterior lobe at this time point and were found in all lobes in an age-dependent manner thereafter. No metastasis was apparent at any age. Additional carcinogen treatment or castration did not enhance progression or generate selective growth of hormone-independent prostate cancer cells. These results suggest that our TG rats are suitable for clarification of mechanisms in early stages of prostate carcinogenesis, that is, from prostatic intraepithelial neoplasia (PIN) to non-invasive and then invasive lesions.

Adenocarcinoma↗

PubMed2003

Lack of carcinogenic risk in the prostate with transplacental and lactational exposure to bisphenol A in rats.

The current study was designed to examine the modulating effects of bisphenol A (BPA) on prostate cancer risk in male offspring exposed transplacentally and lactationally. BPA was administered to F344 female rats by gavage at 0, 0.05, 7.5, 30, 120 mg/kg/day during pregnancy and lactation periods. When F1 males reached 5 weeks old, they were given 10 subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or corn oil vehicle and rats were then sacrificed under ether anesthesia at week 60. There were no observable effects on the accessory sex organ weights of male offspring. Transplacental and lactational exposure to BPA did not affect the incidences of preneoplastic and neoplastic lesions in the accessory sex organs (prostate and seminal vesicle) of F1 rats and did not induce any proliferating lesions without DMAB. Our data suggest that maternal exposure to BPA during the period of pregnancy and lactation does not affect the risk of prostate carcinogenesis in male offspring.

Administration, Oral↗

PubMed2002

Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats by fenbendazole--a CYP1A2 inducer.

Fenbendazole (FBZ) is an anthelmintic drug known to be a potent CYP1A2 inducer. Combined effects of FBZ on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats were investigated using a medium-term liver bioassay system. No modifying influence was found in terms of glutathione S-transferase placental-form positive foci development although CYP1A2 protein expression in the livers of rats that were given MeIQx and FBZ was 2.3-fold higher than with MeIQx alone. NAT2 mRNA expression did not differ among the groups as revealed by quantitative reverse transcriptase-polymerase chain reaction analysis. These results suggest that elevated CYP1A2 expression is not sufficient to enhance MeIQx-induced hepatocarcinogenesis.

Animals↗

PubMed2002

DNA methylation in the androgen receptor gene promoter region in rat prostate cancers.

BACKGROUND: Invasive adenocarcinomas developing in the rat dorsolateral prostate on combined treatment with 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP) are biologically androgen-independent and lacking androgen receptor protein (AR) expression. The present study was conducted to assess the mechanisms underlying this loss of AR expression in rat prostate cancer. METHODS: The methylation status of the AR gene promoter region in rat prostate cancer and cell lines (PLS10, 20, and 30) was examined by Southern blotting, methylation-specific polymerase chain reaction, and methylation-sensitive single-strand conformation analysis (MS-SSCA). RESULTS: AR mRNA expression was not detected in any of the rat prostate cancers or cancer cell lines tested by Northern blot analysis. Higher levels of methylated CpGs were observed in PLS20 than PLS10 or 30. Demethylation treatment by 5-aza-2'-deoxycytidine restored AR mRNA expression in PLS20. The CpGs suggested to be responsible for AR expression in rat prostate cancer were found to be located -9 and -1 nucleotides upstream of the transcriptional initiation site. All of the examined rat prostate and seminal vesicle cancers demonstrated hypermethylation at these CpG sites. CONCLUSIONS: These data clearly demonstrate that aberrant hypermethylation in the AR promoter region may play a critical role in AR expression in rat prostate cancers.

Adenocarcinoma↗

PubMed2002

Down-regulation of human X-box binding protein 1 (hXBP-1) expression correlates with tumor progression in human prostate cancers.

BACKGROUND: In our previous study, the gene encoding the human X-box binding protein 1 (hXBP-1) was isolated as a down-regulated gene in advanced prostate cancers using cDNA-representational difference analysis (RDA). In the present investigation, we characterized alterations of hXBP-1 in prostate cancer specimens. METHODS: Expression patterns of hXBP-1 in a series of human prostate cancers were examined by Northern blotting, mRNA in situ hybridization or immunohistochemistry. Loss of heterozygosity (LOH) analysis using microsatellite markers and gene mutation analysis in the hXBP-1 region were also performed. RESULTS: Expression of hXBP-1 was localized in epithelial and adenocarcinoma cells of the prostate. An inverse correlation between hXBP-1 expression and histological differentiation was found in a series of prostate cancers without hormonal therapy. Majority of refractory cancer cases exhibited weak hXBP-1 expression. No allelic loss or gene mutations were found in the hXBP-1 region and its open reading frame, respectively, in the prostate cancer examined. CONCLUSIONS: These results suggest that reduction of hXBP-1 expression may be a useful marker for prostate adenocarcinoma differentiation and progression.

Adenocarcinoma↗

PubMedDate not supplied

Renal toxicity induced by folic acid is associated with the enhancement of male reproductive toxicity of di(n-butyl)phthalate in rats.

Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.

Animals↗