RESUMO
Previous studies reported the presence in rat mammary tissue of a cytosolic xanthine oxidoreductase pathway for the metabolism of alcohol to acetaldehyde and hydroxyl radicals and to the microsomal biotransformation of ethanol to acetaldehyde. It was also reported that after chronic ethanol drinking stressful oxidative conditions can be observed. The present work reports that even after single doses of ethanol, given at three different levels (6.3 g kg(-1); 3.8 g kg(-1) or 0.6 g kg(-1) p.o.), acetaldehyde accumulates for prolonged periods of time in the mammary tissue to reach concentrations higher than in blood (e.g. 5.1+/-1.2 nmol g(-1) versus 0.2+/-0.1 nmol ml(-1), for 6.3 g kg(-1) dose, 6 h after intoxication). The presence in rat mammary tissue of low activities of additional enzymes able to generate acetaldehyde was established (alcohol dehydrogenase: 0.97+/-0.84 mU mg(-1) protein; CYP2E1: 1.30+/-0.12 x 10(-2) pmol 4-nitrocatechol min(-1) mg(-1) protein) and a low activity of aldehyde dehydrogenase was observed in the cytosolic, mitochondrial and microsomal fractions (0.02+/-0.04; 0.35+/-0.09 and 0.72+/-0.19 mU mg(-1) protein, respectively). After a single high dose of ethanol, an increased susceptibility to oxidative stress was observed, as evidenced by changes in the shape of t-butylhydroperoxide induced emission of chemiluminescence in mammary tissue (6.3 g kg(-1) dose; at 3 and 6 h). In summary, the results show that even after single doses of ethanol, acetaldehyde, either formed in situ or arriving via blood, tends to accumulate in mammary tissue and that this condition might decrease cell defenses against injury.
Assuntos
Acetaldeído/metabolismo , Depressores do Sistema Nervoso Central/farmacocinética , Depressores do Sistema Nervoso Central/toxicidade , Etanol/farmacocinética , Etanol/toxicidade , Glândulas Mamárias Animais/metabolismo , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Depressores do Sistema Nervoso Central/sangue , Citocromo P-450 CYP2E1/metabolismo , Relação Dose-Resposta a Droga , Etanol/sangue , Feminino , Medições Luminescentes , Estresse Oxidativo/efeitos dos fármacos , Ratos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/enzimologiaRESUMO
CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.
Assuntos
Citocromo P-450 CYP1A1/genética , Glutationa S-Transferase pi/genética , Neoplasias Bucais/genética , Neoplasias de Células Escamosas/genética , Polimorfismo Genético/genética , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/enzimologia , Neoplasias de Células Escamosas/enzimologia , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95 percent CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95 percent CI = 0.70-2.79) with OSCC.