RESUMO
Preliminary evidence suggests that genetic polymorphisms in certain enzymes involved in xenobiotic metabolism and chemical defense could modify a susceptibility to prostate cancer. In the present study, two recently described phenol sulphotransferase SULT1A1 alleles (SULT1A1*1, SULT1A1*2) were investigated using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Genotyping was performed on DNA isolated from white blood cells from 134 patients with prostate cancer and 184 healthy control subjects. Both the prostate cancer patients and the controls demonstrated similar frequencies of the variant allele SULT1A1*2 (35.1% vs 39.1%). Homozygosity for the variant allele was slightly less frequent in cancer patients than controls (12.7% vs 17.4%). Our study does not support the hypothesis that the phenol sulphotransferase variant allele SULT1A1*2 with a G/A transition at nucleotide 638 is a risk modifier for prostate cancer in the Caucasian population.
Assuntos
Arilsulfotransferase , Polimorfismo Genético , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Sulfotransferases/genética , Alelos , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
METHODS: Three-month-old female Wistar rats were fed with 20% alcohol in their drinking fluid over 6-17 mo using an interrupted feeding regimen. At different times, pancreatic acini were isolated by mild collagenase digestion. The concentrations of inositol-1,4,5-trisphosphate (1,4,5-IP3) were determined by a specific radioreceptor assay, before and at different times after stimulation with varying concentrations of CCK-8. CCK-induced dynamics of cytoplasmic calcium ([Ca2+]c) was investigated in acinar cells by confocal laser raster microscopy. Acinar alpha-amylase (Aml) secretion was measured as enzyme activity in the medium compared to the total activity in the suspension. RESULTS: In 12-13-mo-old rats, the CCK-stimulated 1,4,5-IP3 formation in acini was found to be decreased compared to young rats (age 4 mo). In rats of the same age fed with ethanol from the age of 3 mo on, 1,4,5-IP3 concentrations in acini were higher and reached values comparable to those in young rats. Correspondingly, the CCK-induced [Ca2+]c dynamics in acini isolated from 9-mo-old rats was impaired compared to that of young rats but normal in aged, chronically alcohol-fed rats. Aml secretion under CCK stimulation, however, which was decreased in aged rats, was additionally impaired after alcohol feeding. CONCLUSION: Chronic alcohol feeding modifies 1,4,5-IP3 formation, the [Ca2+]c dynamics of, and the Aml secretion of rat pancreatic acini in response to CCK stimulation. Obviously, the age-related impairment of 1,4,5-IP3 formation and [Ca2+]c dynamics is improved. In contrast, the decrease in Aml secretion of acini isolated from aged rats is more pronounced after long-term alcohol-feeding.