High and low fluences of alpha-particles induce a G1 checkpoint in human diploid fibroblasts.

نویسندگان

  • E I Azzam
  • S M de Toledo
  • A J Waker
  • J B Little
چکیده

The effects of exposure to high and very low fluence alpha-particles on the G1 checkpoint were investigated in human diploid fibroblasts irradiated and released from density-inhibited confluent cultures by the use of the cumulative labeling index method. Transient and permanent arrests in G1 occurred in fibroblast populations exposed to mean doses as low as 1 cGy, suggesting that nontraversed bystander cells may contribute to the low dose response. In cells exposed to high fluences, the G1 checkpoint is at least as extensive as in gamma-irradiated cells. In contrast to gamma-irradiated cells, neither repair of potentially lethal damage nor a reduction in the fraction of cells transiently or permanently arrested in G1 were observed in cells held in confluence for 6 h after alpha-particle irradiation. Studies with isogenic wild-type, p53-/-, and p21Waf1-/- mouse embryo fibroblasts exposed to either gamma or alpha-particle radiation revealed a total lack of G1 arrest in either p53-/- or p21waf1-/- cells, indicating that the G1 checkpoint in wild-type cells is p53-dependent and that p21Wf1 fully mediates the role of p53 in its induction. In contrast to human cells, mouse embryo fibroblasts do not undergo a permanent G1 arrest. Except under conditions favoring potentially lethal damage repair, a comparable expression pattern of p53, p21Waf1, and other cell cycle-regulated proteins (pRb, p34cdc2, and cyclin B1) was observed in alpha-particle or gamma-irradiated human fibroblasts.

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

High and Low Fluences of a-Particles Induce a G1 Checkpoint in Human Diploid Fibroblasts

The effects of exposure to high and very low fluence a-particles on the G1 checkpoint were investigated in human diploid fibroblasts irradiated and released from density-inhibited confluent cultures by the use of the cumulative labeling index method. Transient and permanent arrests in G1 occurred in fibroblast populations exposed to mean doses as low as 1 cGy, suggesting that nontraversed bysta...

متن کامل

Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G1 Checkpoint in a G0-like State of Quiescence

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40-45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from...

متن کامل

Oxidative metabolism modulates signal transduction and micronucleus formation in bystander cells from alpha-particle-irradiated normal human fibroblast cultures.

The role of oxidative metabolism in the up-regulation/activation of stress-induciblesignaling pathways as well as induction of micronucleus formation in bystander cells was investigated. By immunoblotting and in situ immunofluorescence, active Cu-Zn superoxide dismutase (SOD) enzyme and active catalase enzyme were shown to inhibit the up-regulation of p21(Waf1) as well as the induction of micro...

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

Inactivation of G2 checkpoint function and chromosomal destabilization are linked in human fibroblasts expressing human papillomavirus type 16 E6.

Chromosomal stability was linked to G2 checkpoint function in human fibroblasts expressing the human papillomavirus type 16 E6 oncoprotein. Soon after expression of E6, cells displayed an undamaged, diploid karyotype and normal mitotic delay after gamma-irradiation. As the E6-expressing cells aged through their in vitro life span, G2 checkpoint function diminished progressively. After 30-70 pop...

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 60 10  شماره 

صفحات  -

تاریخ انتشار 2000