The production of chromosome structural changes by radiation

This paper attempts an update and comment upon some of the topics of chromosome aberration formation which Lea raised in Chapter VI of his classic work 'Actions of Radiations on living Cells'. Only the first nine sections of this chapter are covered, which deal primarily with the qualitative aspects of aberrations, their formation, classification and interrelationships. In commenting upon these topics, pertinent references are made to work with mammalian and human cells. Increased knowledge of the importance of DNA as a fundamental target and the integral part it plays in the complex structure of the chromosome, coupled with cellular techniques not available to these earlier workers necessitate some revision and modification of early ideas. However, inspite of the enormous accumulation of data and ideas since the original work was published in 1946, the foundation that these early workers laid is still very solid. Surprisingly, we are still puzzled by many of the problems that perplexed them.     

Loss of antibody production accompanied by chromosome loss in a cloned hybrid line secreting antibodies to sheep red blood cells

Summary Somatic cell hybrids between Sp2/O-Ag14 mouse myeloma cells and lymphocytes derived from BALB/c mice hyperimmunized with sheep red blood cells (SRBC) were produced. One hybrid producing IgG₁ antibody to SRBC was selected, cloned twice and subsequently transferred to BALB/c mice. After a number of transfers it was found that the antibody titer in ascitec fluid gradually decreased. Cytogenetic analysis revealed gradual chromosome loss in the hybrid clone, which produced progressively less antibody.     

Induction of chromosomal aberrations by the anthracycline antitumor antibiotics N,N-dimethyldaunomycin and aclacinomycin A

Summary The clastogenic effect of the anthracycline antitumor antibiotics, N,N-dimethyldaunomycin and aclacinomycin A, was studied in a murine hemopoietic cell line (Friend leukemia cells). A dose-dependent increase in chromatid lesions, i.e., achromatic lesions, chromatid breaks, chromatid deletions and triradial or quadriradial chromosomal exchange figures, was found. It appears that the clastogenicity of N,N-dimethyldaunomycin and aclacinomycin A is lower than that of the classic anthracycline, daunomycin, which is also a potent mutagen and carcinogen. The data demonstrate that the capacity of chemicals to induce point mutations and chromosomal aberrations may not necessarily be correlated: aclacinomycin A is devoid of mutagenic activity in bacterial (Salmonella typh.) and mammalian cell (HGPRT) mutagenesis assays, and is non-carcinogenic in rats. Nevertheless, it was now found to possess clastogenic activity.     

Increase in the survival time of mice exposed to ionizing radiation by a new class of free radical scavengers

Summary N-acyl dehydroalanines react with and scavenge mainly superoxide radical and hydroxyl radical (HO^.). The ortho-methoxyphenylacetyl dehydroalanine derivative, indexed as AD-20, protects mice against damage resulting from total body X-irradiation, as measured by the increase in their survival time. AD-20 increases the LD₅₀ at 30 days from 6.1 to 7.3 Gy in animals exposed to a wide range of X-rays (6 to 10 Gy). The dose reduction factor (D R F) of AD-20 is 1.20. We postulate that such radioprotective effect may result from its free radical scavenging activity.     

Induction of chromosome aberrations and chlorophyll mutations in plants by methylisocyanate (MIC) gas

Summary Seeds ofSolanum surattense Burm. f. collected from areas of Bhopal (India) affected by methylisocyanate gas showed chromosome aberrations in root cells, and growth retardation and chlorophyll mutation of seedlings, the frequencies of which varied from one locality to another.     

Decompoisition of toxic and environmentally hazardous 2,3,7,8-tetra-chlorodibenzo-p-dioxin by gamma irradiation

Summary The decomposition of the toxic and environmentally hazardous 2378-TCDD by gamma irradiation was studied and successfully used to decontaminatge laboratory wastes containing small quantities of this chemically and biological stable compound. The method makes use of gamma irradiation from a commercial⁶⁰cobalt facility at high dose levels (100 kGy) to break down the compound into notoxic products. Irradiation also decomposed 2378-TCDD in contaminated soil from the Seveso accident.     

Storage of irradiated human blood; a source of error in quantitative chromosome analysis

Summary Human whole blood was irradiated with 2.5 Gy of 220 kVp X-rays and stored before culture with 9.7 M BrdU and 19.4 or 38.7 M BrdU for 0, 24, 48 and 72 h. The frequency of dicentrics and ring chromosomes was determined in cells staining as first division (M1) metaphases with the fluorescence plus Giemsa technique. Storage had no influence on the observed aberration yields in 44 h cultures containing 9.7 M BrdU. In 66 h cultures at 19.4 M BrdU the observed yields after 2 and 3 days' storage were significantly lower as compared to cultures from fresh blood. No storage effect was revealed in 66 h cultures containing 38.7 M BrdU. In cases where cytogenetic radiation dosimetry has to be carried out using blood samples which have been in transit for 2–3 days, the findings are of relevance for a correct determination of the chromosome damage in M1 cells.     

Biological effectiveness of solar UV radiation in humans

Solar UVB radiation is prejudicial to the health of humans in a number of ways. Erythema and photodermatoses are acute reactions of the skin; keratitis and conjunctivitis are acute reactions of the eye. Various types of skin cancer, accelerated aging of the skin, and cataract formation in the crystalline lens are reactions that appear with great latency. UV radiation can also cause damage to the immune system and DNA. For the period 1981–1991, an increase in erythemal effective UVB radiation of +(7±4)% per decade was measured in a non-pulluted high mountain area (Jungfraujoch, 3576m a.s.l., Switzerland). This increase is related to a decrease in stratospheric ozone. The effects on human health are discussed. A 10% ozone reduction increases non-melanoma skin cancer by 26% and cataract by 6 to 8%.     

Enhancement of the cytogenetic efficacy of the antitumor agent bleomycin by the calcium and calmodulin antagonist fendiline

Summary The induction of chromosome aberrations (dicentric and ring chromosomes) in human lymphocytes by the antitumor agent bleomycin is synergistically enhanced when bleomycin is applied together with the calcium antagonist fendiline (Sensit^®).     

The potency of heparin-like activity of glycosaminoglycans released by human endothelial cells in culture

Summary Glycosaminoglycans isolated from culture medium conditioned by human endothelial cells showed heparin-like antithrombin III cofactor activity measured by Xa inhibition. Their activity was relatively weak, 0.1% of the potency of heparin, but was approximately 5-fold more potent than that of glycosaminoglycans derived from vascular smooth muscle cells.     

The consequences of the discovery by W. C. Röntgen for present-day medical physics and radiation protection

When the German physicist W. C. Röntgen discovered X-rays, which were named after him, he introduced a new development in medicine and biology: together with the discoveries of A. H. Becquerel and M. Curie, radiology with its diagnostic and therapeutic methods was made possible. The medical physicist has an important task to fulfill in modern radiotherapy, nuclear medicine and radiodiagnostics. The longtime interdisciplinary collaboration has won the international recognition of medical physics as a scientific discipline, a health care profession and a university subject. Several incidents, including contemporary ones, show that the efforts made towards radiation protection must remain an important domain of the specialist.     

Effect of steviol and its structural analogues on glucose production and oxygen uptake in rat renal tubules

Summary The effect of several natural products ofStevia rebaudiana on glucose production and oxygen uptake in rat renal cortical tubules was investigated. Steviol, isosteviol and glucosilsteviol decreased glucose production and inhibited oxygen uptake. The sweet principle stevioside, and steviolbioside, however, were without effect on gluconeogenesis and oxygen uptake.     

Demonstration of the structural connections of the longitudinal muscle cells and circular muscle cells,and interconnections between the two,in the alimentary canal of an oligochaete,Branchiura sowerbyi B.

Summary The longitudinal and circular muscle cells of the alimentary canal of the oligochaete wormBranchiura sowerbyi show intercell couplings. These couplings occur between adjoining cells of the same or of the other orientation.We wish to thank Dr S. Kawaguti, Prof. emeritus of Okayama University, for his kind advice.     

Differential protection of radiation-induced DNA single-strand breaks and cell survival by solcoseryl

Summary V79 Chinese hamster cells were studied in vitro for modification of cobalt-60 gamma radiation effects by solcoseryl. This treatment did not modify cell survival but did protect against DNA single-strand breaks.Solcoseryl is a registered trademark of Solco Basle Ltd, CH-4127 Birsfelden, Switzerland and was kindly supplied by Drs Haigis and Nasrin. In scientific German literature this material is referred to as Actihaemyl.Supported in part by U.S. Department of Energy Contract No. W-31-109-ENG-38 and NIH/NCI grant No. CA-37435, awarded to D. Grdina, ANL.     

The genetics of phytotoxin production by plant pathogenic fungi

Little is known about the genetic control of phytotoxin production by plant pathogenic fungi. The production of host-selective toxins known to play a role in disease development has been genetically analyzed in three species ofCochliobolus. InC. heterostrophus, a single genetic locus with two alleles has been identified controlling the production of HMT-toxin. This locus appears to be at or near the breakpoint of a chromosome rearrangement. Single genetic loci have also been identified controlling the production of HC-toxin byC. carbonum and HV-toxin byC. victoriae. The locus inC. carbonum may be a cluster of tightly linked genes.     

The role of zinc in regulating tabtoxin production

Summary The phytotoxin, tabtoxinine--lactam, is produced by severalPseudomonas syringae pathovars if adequate Zn is available, otherwise its biologically inactive form, tabtoxin, is produced. The Zn is required for the action of a peptidase which cleaves tabtoxin, releasing the toxic -lactam.This research was supported in part by U.S.D.A. Competitive Research Grant No. 83-CRCR-1-1201.     

The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen

The life of aerobes is dependent on iron and oxygen for efficient bioenergetics. Due to potential risks associated with iron/oxygen chemistry, iron acquisition, concentration, storage, utilization, and efflux are tightly regulated in the cell. A central role in regulating iron/oxygen chemistry in animals is played by mRNA translation or turnover via the iron responsive element (IRE)/iron regulatory protein (IRP) system. The IRE family is composed of three-dimensional RNA structures located in 3′ or 5′ untranslated regions of mRNA. To date, there are 11 different IRE mRNAs in the family, regulated through translation initiation or mRNA stability. Iron or oxidant stimuli induce a set of graded responses related to mRNA-specific IRE substructures, indicated by differential responses to iron in vivo and binding IRPs in vitro. Molecular effects of phosphorylation, iron and oxygen remain to be added to the structural information of the IRE-RNA and IRP repressor in the regulatory complex. Received 21 April 2007; received after revision 13 July 2007; accepted 2 August 2007     

The processing and presentation of endogenous and exogenous antigen by Schwann cells in vitro

The expression of major histocomatibility complex class II in vitro and in vivo by Schwann cells indicates a potential facultative role of Schwann cells in the presentation of antigen to neuritogenic T cells during inflammatory demyelinating neuropathies. Using a T cell proliferation assay, this study demonstrated that processing and presentation of endogenous and exogenous antigen by Schwann cells influences T cell proliferation. Statistical analysis of proliferation and its relation to processing and presentation of antigen by Schwann cells had not been previously addressed. Different combinations of factors including treatment of cultures (untreated, irradiated or fixed), concentration of exogenous antigen (0 or 40 μmg/ml), the presence of interferon-γ and the timing of exogenous antigen addition influence the proliferation P₂-specific, non-mammalian protein ovalbumin-specific T cell lines and naive T cells. Received 25 July 2002; received after revision 9 September 2002; accepted 7 October 2002     

The ovicidal activity ofcis-dehydromatricaria ester: time-dependance of its enhancement by UV light

Summary Freshly laid eggs ofDrosophila melanogaster were treated with the polyacetylenic compoundcis-dehydromatricaria ester. The toxicity of the chemical was enhanced by treatments with long-wavelength ultraviolet light, and the maximum effect was observed when the UV irradiation was performed 4–5 h after the initial contact of the eggs with the chemical.We are grateful to Professor E. Spiess for advice and assistance, and to the National Institutes of Health (GM 24144) for financial support.