Modulatory effect of glucose-6-phosphate dehydrogenase deficiency on benzo(a)pyrene toxicity and transforming activity for in vitro-cultured human skin fibroblasts.

نویسندگان

  • F Feo
  • L Pirisi
  • R Pascale
  • L Daino
  • S Frassetto
  • R Garcea
  • L Gaspa
چکیده

Human skin fibroblasts isolated in vitro from subjects carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase exhibit an 85% decrease of this enzymatic activity. There is a 26% and a 94% decrease of the hexose monophosphate shunt and of the reduced nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate ratio, respectively. Incubation with 0.1 mM methylene blue activates the hexose monophosphate shunt 7 times that of normal fibroblasts and only 2.2 times that of glucose 6-phosphate-deficient cells. This behavior is coupled with an increase of the resistance to cell death induced by benzo(a)pyrene, a carcinogen, the activation of which proceeds through a reduced nicotinamide adenine dinucleotide phosphate-dependent arene oxide formation. In contrast, no difference between the normal and the deficient fibroblasts exists as regards the toxic effect of methylnitrosourea, a carcinogen that does not need metabolic activation. A growth-retarding effect of benzo(a)pyrene was observed in both normal and deficient cells during 9 days in vitro. This effect is lower in the fibroblasts carrying the Mediterranean glucose-6-phosphate dehydrogenase variant. Glucose-6-phosphate dehydrogenase deficiency protects human fibroblasts against the benzo(a)pyrene-induced in vitro transformation. This effect is mimicked by the incubation of normal fibroblasts with dehydroepiandrosterone, a strong inhibitor of glucose-6-phosphate dehydrogenase. The deficiency of this enzymatic activity, either genetically transmitted or induced by dehydroepiandrosterone, is coupled with a reduced rate of benzo(a)pyrene conversion to water-soluble metabolites by human skin fibroblasts.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Protective Effect of Quercetin on Oxidative Stress in Glucose-6-Phosphate Dehydrogenase-Deficient Erythrocytes in Vitro

Glucose-6-phosphate dehydrogenase (G6PD) deficient subjects are vulnerable to oxidative stress. Quercetin, a flavonoids, has been employed as a potent oxygen-free radical scavenger in order to assess the protective effects of quercetin against H2O2-induced oxidative damage in G6PD-deficient and normal human erythrocytes. Erythrocytes of G6PD-deficient (n = 10) and normal (n = 10) subjects were ...

متن کامل

Effect of Low–Level Helium-Neon Laser Irradiation on the Release of Interleukin 6 and Basic Fibroblast Growth Factor from Cultured Human Fibroblasts in High Glucose Medium

Purpose: Low level laser therapy is suggested as a new therapeutic method in diabetic wound healing. This survey aimed to evaluate the effects of low level laser on human fibroblasts cultured in high glucose cultures. Materials and Methods: The human skin fibroblasts were cultured under standard condition. The cells were cultured in high glucose culture medium (15mM/L) for a week and two weeks ...

متن کامل

Protective Effect of Quercetin on Oxidative Stress in Glucose-6-Phosphate Dehydrogenase-Deficient Erythrocytes in Vitro

Glucose-6-phosphate dehydrogenase (G6PD) deficient subjects are vulnerable to oxidative stress. Quercetin, a flavonoids, has been employed as a potent oxygen-free radical scavenger in order to assess the protective effects of quercetin against H2O2-induced oxidative damage in G6PD-deficient and normal human erythrocytes. Erythrocytes of G6PD-deficient (n = 10) and normal (n = 10) subjects were ...

متن کامل

Prevalence of Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Jiroft City in Southern Iran

Background and Aims: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a global problem and the most common cause of jaundice in neonates. Hence, this study was conducted to investigate the prevalence of G6PD deficiency in Jiroft city in southern Kerman. Materials and Methods: This descriptive cross-sectional study was carried out from 2016 to 2019. Blood samples were taken from all patie...

متن کامل

P-90: Effect of Phosphodiesterase Type3 Inhibitor, Cilostamide, on The Developmental Competence of Ovine OocytesIsolated by Glucose 6-Phosphate Dehydrogenase Activity

Background: The developmental competence of oocytes matured in vitro (IVM) is yet far below than in vivo counterparts. Recent studies suggest that the asynchrony between nuclear/cytoplasmic maturation and the initial low/heterogeneous quality of oocytes are the most important factors affecting IVM success. We investigated whether selection of growing oocytes (based on their glucose 6- phosphate...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 44 8  شماره 

صفحات  -

تاریخ انتشار 1984