Ionising radiation

p53: A role in the initiation and progression of leukaemia? by B.A. Guinn, and R. A. Padua

ABSTRACT P53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes which control cell growth, DNA repair and apoptosis. p53 mutations have been found in a wide variety of different cancers including all of the different types of leukaemia, with varying frequencies. Many of the point mutations have been localised to the central region of the gene encoding the DNA binding domain and are often found in addition to the deletion or rearrangement of the other allele. The loss of normal p53 function results in genomic instability and uncontrolled growth of the host cell. In addition hemizygously mutated p53 may exhibit gain of function properties such as immortalisation and the ability to co-operate with other oncogenes such as RAS to transform cells. p53 mutations appear to be associated with disease progression and poor prognosis. As a target for therapy p53 shows promise. This review seeks to describe the involvement of p53 in haematological malignancies.
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Induction of genomic instability in normal human bronchial epithelial cells by 238Pu [alpha]-particles by CH. Kennedy, CE. Mitchell, NH. Fukushima, RE. Neft and JF. Lechner ("Carcinogenesis", V 17, Issue 8, Dec 1996, pp 1671--1676)

ABSTRACT Pulmonary deposition of [alpha]-particle-emitting radon daughters is estimated to account for 10% of all lung cancer deaths in the USA. However, the nature and timing of early (preneoplastic) genetic alterations in radon-associated lung cancer are still relatively uncertain. The purpose of this investigation was to determine whether genomic instability occurs after exposure of cultured normal human bronchial epithelial cells to six equal, fractionated doses of [alpha]-particles (total doses 2-4 Gy). Two weeks after the final exposure, foci of phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control, low and high dose cultures respectively. Of these, 18% exhibited extended lifespans relative to unexposed controls. Elevated frequencies of binucleated cells (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC cultures from the low and high dose groups respectively. The micronucleus assay also showed evidence of genomic instability in 40 and 38% of PAC cultures from the low dose and high dose groups respectively. No changes in microsatellite length, another marker of genomic instability, were detected in any of the PAC samples with the 28 markers used for this assay. However, one PAC (L2) showed a hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest frequency of cells containing micronuclei (MN), exhibited a hemizygous deletion at 7q31.3. Each loss may represent a stable mutation that resulted either directly from irradiation or later in progeny of exposed cells because of [alpha]-particl e-induced genomic instability. The fact that elevated levels of BNCs and MN were present in the progeny many generations after irradiation indicates that the genetic alterations detected with these two markers were not a direct consequence of radiation exposure, but of resulting genomic in stability, which may be an early change after exposure to [alpha]-particles.

RADIATION RESEARCH Volume 146, Number 3, September 1996

See William F. Morgan, Joseph P. Day, Mark I. Kaplan, Eva M. McGhee and Charles L. Limoli "Genomic Instability Induced by Ionizing Radiation" p. 247. This review summarizes the current literature concerning genomic instability induced by ionizing radiation. Special emphasis is given to the potential events which initiate and perpetuate this phenotype, and to the multiple delayed effects of exposure to such radiations.

Ionising radiation (excerpts from "Human Cancer: epidemiology and environmental causes")

Detrimental effects of exposure to ionising radiation, including toxicity, burns and tumour induction, became noticeable very early in the history of radiation. Many pioneers in radiation research died of neoplasms, among them Thomas Edison's assistant and Marie Curie. This pattern became clear in the 1940s with the observation of a high incidence of leukemia among radiologists. In the 1930s a high incidence of osteosarcoma was noted among luminous dial painters, who were in the habit of licking the point of their paint-brushes, to make them thinner, thus ingesting radium (Rowland et al 1978). In the 1950s a high incidence of leukemia was also detected among the survivors of the atomic bombings at Hiroshima and Nagasaki (Folley et al., 1952) and among patients treated with X-rays for ankylosing spondylitis (Court Brown & Doll, 1957).

Advances in the Treatment of Radiation Injuries (excerpts)

Findings concerning the complex nature of radiation injuries and of potential prevention, assessment, and treatment strategies were reported at the April 1993 Second Consensus Development Conference on the Treatment of Radiation Injuries. The conference, conducted in Bethesda, Maryland, was sponsored by the Armed Forces Radiobiology Research Institute and was supported in part by educational grants from Amgen, Inc., Thousand Oaks, California; Immunex Research and Development Co., Seattle, Washington; US Bioscience, Conshohocken, Pennsylvania; Monsanto/GD Searle Co., St. Louis, Missouri; Sandoz Cytokine Development Unit, East Hanover, New Jersey; and Nycomed/Bioreg Co., Oslo, Norway.

Health Physics and Protection (from PSU.Edu)

The legion of early X-ray martyrs constitutes a constant testament to the need for adequate understanding of protection and risk in radiation oncology. The evolution of standards in the field includes the adoption of the radium standard (1911), principles of maximum tolerable doses (1921), the roentgen (1928), and the rad (1953). Advances in basic understanding of genetically significant and maximally permissible doses has led contemporary radiation oncologists to carefully monitor for adverse effects in cancer therapy and in resurgent applications in benign conditions.

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