60 research outputs found
Ionizing Radiation and Chronic Lymphocytic Leukemia
The U.S. government recently implemented rules for awarding compensation to individuals with cancer who were exposed to ionizing radiation while working in the nuclear weapons complex. Under these rules, chronic lymphocytic leukemia (CLL) is considered to be a nonradiogenic form of cancer. In other words, workers who develop CLL automatically have their compensation claim rejected because the compensation rules hold that the risk of radiation-induced CLL is zero. In this article we review molecular, clinical, and epidemiologic evidence regarding the radiogenicity of CLL. We note that current understanding of radiation-induced tumorigenesis and the etiology of lymphatic neoplasia provides a strong mechanistic basis for expecting that ionizing radiation exposure increases CLL risk. The clinical characteristics of CLL, including prolonged latency and morbidity periods and a low case fatality rate, make it relatively difficult to evaluate associations between ionizing radiation and CLL risk via epidemiologic methods. The epidemiologic evidence of association between external exposure to ionizing radiation and CLL is weak. However, epidemiologic findings are consistent with a hypothesis of elevated CLL mortality risk after a latency and morbidity period that spans several decades. Our findings in this review suggest that there is not a persuasive basis for the conclusion that CLL is a nonradiogenic form of cancer
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma
Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor ĪŗB (NF-ĪŗB). NF-ĪŗB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virusāpositive (EBV+) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBVā cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-ĪŗB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-ĪŗB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-ĪŗB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBVā than EBV+ cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis
Izloženost genotoksiÄnim agensima iz životnog okoliÅ”a tijekom prenatalnog razvoja i djetinjstva
Health disorders and diseases related to environmental exposure in children such as cancer and immunologic disturbances (asthma, allergies) are on the rise. However, complex transplacental and prepubertal genotoxicology is given very limited consideration, even though intrauterine development and early childhood may be critical for elucidating the cancer aetiology. The foetus is transplacentally exposed to contaminants in food and environment such as various chemicals, drugs, radiochemically contaminated water and air. Target organs of xenobiotic action may differ between the mother and the foetus due to specific stage of developmental physiology and enzyme distribution. This in turn may lead to different levels of clastogenic and aneugenic metabolites of the same xenobiotic in the mother and the foetus. Adultās protective behaviour is not sufficient to isolate children from radioisotopes, pesticides, toxic metals and metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and various food contaminants, which are just a part of the stressors present in a polluted environment. In order to improve legislation related to foetus and child exposure to genotoxic and possibly carcinogenic agents, oncologists, paediatricians, environmental health specialists, and genotoxicologists should work together much more closely to make a more effective use of accumulated scientific data, with the final aim to lower cancer incidence and mortality.UnatoÄ velikim naporima da se smanji okoliÅ”na izloženost u djece se dalje bilježi trend porasta pojavnosti karcinoma i imunosnih poremeÄaja (astma, alergije). Premda su intrauterini razvoj i rano djetinjstvo kritiÄno razdoblje za tumaÄenje etiologije nastanka karcinoma, transplacentalna i prepubertetna genotoksikologija
do danas su slabo istražene. Fetus je transplacentalno izložen brojnim fizikalnim i kemijskim Äimbenicima: kontaminantima iz hrane i okoliÅ”a, radiokemijski kontaminiranoj vodi, zraku te lijekovima. Ciljna tkiva za djelovanje ksenobiotika mogu biti razliÄita u majke i fetusa zbog razliÄitosti u razvojnoj fiziologiji i distribuciji enzima. Zbog toga u organizmu majke i fetusa mogu nastati razliÄite razine klastogenih i aneugenih metabolita istog ksenobiotika.
ZaÅ”titna uloga odraslih u namjeri da sprijeÄe negativne utjecaje oneÄiÅ”Äenog okoliÅ”a na djetetovo zdravlje Äesto je ograniÄena jer su radioizotopi, olovo, PCB, pasivno puÅ”enje, živa, endokrino aktivne tvari, pesticidi i kontaminanti prisutni u svim životnim podruÄjima tijekom razvoja i rasta djeteta. Kako bi se poboljÅ”alo zakonodavstvo vezano uz izloženost djece genotoksiÄnim i vjerojatno kancerogenim tvarima, tijekom razvoja potrebna je bolja suradnja onkologa, pedijatara, struÄnjaka zdravstvene ekologije i genotoksikologa.
Na taj naÄin ostvarilo bi se uspjeÅ”nije iskoriÅ”tavanje postojeÄih znanstvenih podataka u cilju smanjenja incidencije karcinoma i mortaliteta
TRANSURANIC ISOTOPES AND 90Sr IN ATTIC DUST IN THE VICINITY OF TWO NUCLEAR ESTABLISHMENTS IN NORTHERN GERMANY
Letter to the Editor on āThe Hiroshima/Nagasaki Survivor Studies: Discrepancies Between Results and General Perceptionā by Bertrand R. Jordan
Transuranic isotopes and 90Sr in attic dust in the vicinity of two nuclear establishments in Northern Germany
Attic dust was chosen as the test medium in order to search for traces of man-made bone seeking alpha and beta emitters. The samples were taken from 5 houses in the community of Elbmarsch situated at the river Elbe, adjacent to the KrĆ¼mmel nuclear power plant and the nuclear research center of Geesthacht. Five houses in other regions of northern Germany were taken as a control. 238Pu, 239,240Pu, 241Am, and 244Cm were measured by alpha spectrometry after chemical separation. Additionally, 241Pu was measured by liquid scintillation spectrometry, and the fission product 90Sr was measured in a separate investigation. All nuclides except 244Cm showed activities above the detection limit in the Elbmarsch samples and an elevated mean concentration compared to the control. It can be concluded from the activity ratio 241Am/239,240Pu that the Elbmarsch contamination cannot be accounted for by the background levels of transuranic nuclides resulting from weapons fallout. The derived release of alpha emitters is assumed to have contributed to the induction of a leukemia cluster in children, which was observed in Elbmarsch between 1990 and 1996
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