Pathobiological effects of acrolein in cultured human bronchial epithelial cells.

نویسندگان

  • R C Grafström
  • J M Dypbukt
  • J C Willey
  • K Sundqvist
  • C Edman
  • L Atzori
  • C C Harris
چکیده

The ability of the highly reactive aldehyde acrolein to affect growth, membrane integrity, differentiation, and thiol status and to cause DNA damage has been studied at serum- and thiol-free conditions using cultured human bronchial epithelial cells. Acrolein markedly decreases colony survival at 3 microM whereas about 10-fold higher concentrations are required to increase membrane permeability, measured as uptake of trypan blue dye. Acrolein at micromolar concentrations also causes epithelial cells to undergo squamous differentiation as indicated by decreased clonal growth rate, dose-dependent increased formation of cross-linked envelopes, and increased cell planar surface area. Acrolein causes a marked and dose-dependent cellular depletion of total and specific free low-molecular-weight thiols as well as protein thiols. Exposure to acrolein did not cause oxidation of glutathione indicating that thiol depletion occurred by direct conjugation of reduced glutathione to acrolein without concomitant generation of active oxygen species. Furthermore, acrolein is genotoxic and causes both DNA single strand breaks and DNA protein cross-links in human bronchial epithelial cells. The results indicate that acrolein causes several cytopathic effects that relate to multistage carcinogenesis in the human bronchial epithelium.

برای دانلود رایگان 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

Effect of Matrigel on Function and Morphology of Human Endometrial Epithelial Cell in vitro

The importance of extra cellular matrix (ECM) in development and function of different cells has been reported but little is known about its role in human endometrial epithelial cells. The aim of the present study was to examine effects of artificial ECM (Matrigel) and progesterone on the function and morphology of human endometrial epithelial cells in vitro. Methods: Endometrial samples were ...

متن کامل

Polarized and Non-Poarized Human Oviduct Epithelial Cell Ultrastructure in Vitro

Purpose: This study designed to examine polarized culture of epithelial cells from human ovidutc and their ultrastracture under polarizing condition. Materials and Methods: The human oviduct was obtained from patients having undergone total hysterectomy and epithelial cells were isolated using collagenase type I. The epithelial cells were either cultured on ECM (Extracellular matrix) Gel coate...

متن کامل

Acrolein induces heme oxygenase-1 through PKC- δ and PI3K in human bronchial epithelial cells

Heme oxygenase-1 (HO-1) catalyzes the rate limiting reaction of heme metabolism and plays critical roles in resistance to oxidative stress and other cellular functions. It is well known that HO-1 is induced in response to various stresses; however, the signaling pathways involved remains incompletely elucidated. Acrolein is an alpha, beta-unsaturated aldehyde present in cigarette smoke and also...

متن کامل

Acrolein-induced activation of mitogen-activated protein kinase signaling is mediated by alkylation of thioredoxin reductase and thioredoxin 1☆☆☆

Cigarette smoking remains a major health concern worldwide, and many of the adverse effects of cigarette smoke (CS) can be attributed to its abundant electrophilic aldehydes, such as acrolein (2-propenal). Previous studies indicate that acrolein readily reacts with thioredoxin reductase 1 (TrxR1), a critical enzyme involved in regulation of thioredoxin (Trx)-mediated redox signaling, by alkylat...

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

عنوان ژورنال:
  • Cancer research

دوره 48 7  شماره 

صفحات  -

تاریخ انتشار 1988