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Lupus-like syndrome associated with carcinoma of the breast.

Two patients with locally advanced carcinoma of the breast had radiation therapy as primary treatment. Within one year, a lupus-like syndrome developed characterized by pneumonitis, pleural effusion, and positive fluorescent antinuclear antibody (FANA) reaction and lupus erythematosus (LE) preparation. Pericarditis developed in one patient and leukopenia in the other. The bilateral pulmonary disease, serological abnormalities, and rapid and sustained response to administration of prednisone made the diagnosis of systemic lupus erythematosus more likely than radiation-induced disease or metastic carcinoma. Radiation to normal and/or malignant tissue may have initiated an immunological response leading to a lupus-like syndrome.

Adenocarcinoma↗

Isolabelling is a radiation-induced phenomenon.

Human lymphocytes were incubated during two mitotic cycles in the presence of 5-bromodeoxyuridine and differentiation between chromatids was obtained with combined "Hoechst 33258" and azur-eosine staining. Analysis of non-irradiated cells revealed numerous sister chromatid exchanges (SCE) and no abnormalities of "harlequine" appearance of chromosomes. When, however, the cells were irradiated, an identical staining (IS, isostaining) of some chromosomes or chromosome segments were observed. Production of IS was accompanied by decrease of the frequency of SCE, the total frequency of SCE+IS remained, however, the same as in control. An antagonism between SCE and IS was established: the frequency of SCE decreased in the cells with multiple IS, and chromosomes with both SCE and IS were only rarely observed. Thus, IS is neither an artifact nor a physiologic event but a phenomenon induced by radiation. The reliable existence of IS is considered as an evidence for binemic structure of chromatid. It is suggested that some mechanism of lateral spread of genetic information is involved in the production of SCE. If delayed by radiation, the spread could be restricted only to a fraction of chromosome cross-section resulting in IS.

Azure Stains↗

[Modified Giemsa technique for the study of characteristic chromosomes of leukemic C57Bl mice].

G-banded karyotypes have been studied in C57Bl control mice and in animals developing leukemia after i.p. injection of acellular extract of spleen or lymph nodes from isologous animals showing radiation induced leukemia. No visible differences could be detected with respect to the number, size and position of the G-bands between the two groups of animals. From the present observations and from previous work with conventional staining methods, it can be concluded that the development of such leukemia does not involve the presence of chromosome abnormalities.

Animals↗

Radiation-induced erythroleukemia in the beagle dog. A hematologic summary of five cases.

Eleven cases of myeloproliferative disease occurred in a group of 24 beagle dogs placed in a 60Co gamma-ray field at about 13 months of age and irradiated at an exposure rate of 5 R/22-hour day for duratior of life. Of these 11 dogs, 5 (described in this paper) were diagnosed as having erythroleukemia. The bone marrow showed marked erythroblastic hyperplasia, with maturation arrest of the erythroid elements, and increased numbers of myeloblasts and promyelocytes. The terminal peripheral blood was characterized by marked anemia and thrombocytopenia, with circulating erythrocytic precursors and abnormal erythrocyte morphology. Splenomegaly and hepatomegaly occurred in 4 of the 5 animals. In the spleens and livers of all 5, there was extensive leukemic infiltration and proliferation. The extent of leukemic involvement in other tissues and organs varied in individual dogs.

Animals↗

[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones].

The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case.

Aged↗

[Chromosomal abnormalities in human neoplasia (author's transl)].

Multiple connections exist between chromosomal aberrations and malignant tumors. It is the aim of the present article to summarize the data known so far in view of i) cancer-prone chromosome abnormalities, ii) chromosome abnormalities related to tumors and iii) chromosome abnormalities related to carcinogens. In some instances it seemed useful to discuss the findings in man in connection with the results of in vitro experimental data.

Carcinogens↗

Partial deletion of chromosome No. 2 in myelocytic leukemias of irradiated C3H/He and RFM mice.

Chromosomes of mouse myelocytic leukemias that developed in 7 irradiated mice, 3 C3H/He males, 1 RFM female, and 3 RFM males were analyzed with chromosome-banding techniques. Chromosomes No. 2 were partially deleted in 6 of the 7 mice. Although the deleted No. 2 chromosomes varied in size in the 6 mice, one common characteristic was noted in all these deletions: A segment lying between a certain band in the region 2C and a band in the region 2E, including the whole region 2D, was missing. Another consistent abnormality was an addition or a loss of the Y-chromosomes in the fraction of cells in all 6 males. In addition to these consistent abnormalities, various chromosomes had structural abnormalities. The RFM female, which did not have the abnormal No. 2 chromosome, had abnormalities in chromosomes No. 3, 4, 11, 12 and 15 and in the X-chromosome. Of the 20 chromosome pairs, only such chromosomes as No. 1, 5, 8, 14, 17, and 19 and the Y-chromosome did not have the structural abnormalities. The possible role of the partial deletion of the No. 2 chromosome was considered in relation to the development of mouse myeloid leukemias.

Animals↗

Anaplastic cardcinoma of the thyroid in a population irradiated for Hodgkin Disease, 1910--1960.

Post-irradiation carcinoma of the thyroid is usually histologically well-differentiated. In general, those subjects who developed carcinoma had been exposed to low-to-moderate doses of irradiation for benign conditions. We reviewed the charts of 520 patients with Hodgkin's disease seen at Roswell Park Memorial Institute, and found 2 cases of anaplastic carcinoma amongst other thyroidal abnormalities. The existing reports of post-irradiation carcinoma are reviewed and suggestions are made for the management of heavily irradiated, potentially cured patients with Hodgkin's disease.

Adult↗

Cytogenetics of juvenile type chronic granulocytic leukemia.

Cytogenetic examination of bone marrow cells from three patients with juvenile chronic granulocytic leukemia (CGL) showed 46,XX,3p-,11p+ ,t(11p:3p) in one case, 45XY,-E in another, and 45X(X),-C/47,XX,+G in the third. The case with the translocated chromosome originally presented like an acute lymphocytic leukemia (ALL). TAn overt clinical picture of juvenile CGL emerged two and a half years later. Serial study of this case revealed no cytogenetic abnormalities until two years after the diagnosis of ALL, when the translocated chromosome was first observed. Unlike the Ph1 chromosome in adult type CGL, chromosomal abnormalities in juvenile CGL lack specificity, resembling ALL in this respect.

Bone Marrow↗

Second malignancies complicating Hodgkin's disease in remission.

The incidence of second tumours occurring in the course of Hodgkin's disease has been investigated in a series of 452 patients treated with standard chemotherapy or radiotherapy, combination chemotherapy alone, intensive radiotherapy alone, or both intensive radiotherapy and combination chemotherapy administered in sequence. 16 tumours were noted. When analysed according to mode of treatment, 6 cases occurred in a group of 62 patients who received both modalities. When analysed for age, sex, and man-years of follow-up, this group appears to have 14-5 times the risk of developing a second tumour. However, that subgroup which had a complete remission after intensive radiotherapy followed by a relapse of disease, prior to receiving combination chemotherapy, had the highest risk with 18-5 times greater incidence of second tumour than expected. It is noteworthy that, of the 16 second tumours, 2 were acute myeloid leukaemia; in both cases a similar chromosomal abnormality (45 chromosomes, C-group deletion) was noted. The mechanism of oncogenesis may represent a combination of the immunosuppressive effects and cellular effects of those forms of treatment.

Adolescent↗

Acute monocytic leukemia in an irradiated Beagle.

A purebred female Beagle dog that had received 2,000 R of protracted wholebody gamma-irradiation from 60Co when 14 months old had hematologic changes consistent with a myeloproliferative disorder 3 years after the termination of radiation exposure. Peripheral blood and bone marrow findings during the 7-month period before death showed progressive anemia with increased numbers of platelets; immature granulocytes, monocytes and promonocytes. A period of partial remission occurred during which time the peripheral blood was aleukemic, although there was marked thrombocytosis and abnormal erythropoiesis which was evidenced by bizarre circulating nucleated red cells, anisocytosis, poikilocytosis and Howell-Jolly bodies. The dog had a terminal crisis with marked leukocytosis, most cells in the peripheral blood being bizarre monocytes and promonocytes. Tissues obtained at necropsy showed diffuse as well as focal infiltration of the spleen, liver, lymph nodes, heart, kidney and gastrointestinal wall with immature neoplastic cells resembling monocytes and monocytic precursors. The monocytic differentiation of the invasive cell population was confirmed by morphological, cytochemical, histological, ultrastructural and in vitro cell culture studies.

Animals↗

Parathyroid adenomas following irradiation.

Parathyroid adenomas have been demonstrated to occur following external head and neck irradiation. The median latency interval is 30 years. In a series of 74 consecutive patients with histologically diagnosed parathyroid adenomas, 25% gave a history of prior radiation exposure. When compared to a matched control incidence of 7.9%, statistical significance is reached at p less than 0.01. Thyroid abnormalities were present in 68% of the irradiated patients, and 30% of these were malignant. Tumor of skin, breast, and parotid gland also occurrred more frequently than expected. Forty-seven percent of the irradiated group had malignant neoplasms within the radiation field. The histopathology of the radiation-associated parathyroid adenomas is similar to that seen experimentally.

Acne Vulgaris↗

[Correlation between radiological, scintigraphic and histological changes in bone in rabbits following irradiation with single and fractionated doses (author's transl)].

The left hind legs of eight rabbits were irradiated with 1.750 rad in a single dose or with 4,650 rad divided over a period of three weeks. These animals, as well as four who had not been irradiated, were examined periodically radiologically and with 99m Technetium pyrophosphate scintigrams during one year. No difference could be detected between the results of the single and fractionated doses. Scintigraphically there was a biphasic increase in uptake, the first peak co-inciding with the irradiation and of vascular origin, whereas the second peak occurred at four months and was due to a change in bone metabolism. At the end of a year uptake in the irradiated limb was slightly reduced. The earliest radiological changes were found after six months, at the end of the second scintigraphic peak; they consisted of coarsening and blurring of the trabeculae, nonhomogeneous spotty mineralisation and endosteal scalloping. Six animals developed a radiation-induced bone sarcoma, first demonstrated either by scintigraphy or radiology depending on its histology. The value of combining radiological and scintigraphic examinations for the early detection of post-radiation abnormalities is stressed.

Animals↗

Trisomy no. 15 in murine thymomas induced by chemical carcinogens, X-irradiation, and an endogenous murine leukemia virus.

Chromosome banding techniques were used to examine the karyotype of tumor cells from thymic lymphomas induced by three different carcinogens (X-irradiation, polycyclic aromatic hydrocarbons, and an endogenous leukemogenic virus) after injection into neonatal mice of 2 different inbred mouse strains (CFW/D and C57BL/Ka). A total of 89 tumors were studied, and of these 85.4% were characterized by a modal chromosome number of 41. The additional chromosome was the result of a specific abnormality identified as trisomy of chromosome no. 15. The results obtained were independent of the carcinogenic agents and the strain of mouse used. Of the 13 tumors found to have a normal chromosome complement, 4 were induced by X-irradiation and the remaining 9 by the chemical carcinogens. All 15 virus-induced tumors analyzed had a modal chromosome number of 41.

Animals↗

Effects of single dose supervoltage whole brain radiation in Macaca mulatta.

Three groups of four Macaca mulatta were exposed respectively to a single dose of 1000, 1500, and 2000 rads of 20 MeV whole brain radiation with one animal from each group and a control scheduled for sacrifice at 6, 12, 18, and 24 months. With 1000 rads there were no abnormalities. The characteristic lesions in the animals exposed to 1500 and 2000 rads were small foci of delayed radiation necrosis that in the acute phase were relatively large due to marked local accumulation of edema fluid and at later stages were decreased in volume and showed early mineralization. Correspondingly the monkeys frequently showed papilledema, evidently from brain swelling, as the initial clinical finding, and upon histological examination at later stages, brain atrophy and ventricular dilatation. After exposure to 1500 rads the necrotic process was primarily in the white matter of the cerebral hemisphere and progressed from a small number of lesions in this location at 6 months to confluent necrosis at 12 months. At 18 and 24 months, although there was no evidence of further necrosis, there was evidence of increasing gliosis and at 24 months the occurrence of three independent glioblastomas. With exposure to 2000 rads there was a profuse wide scatter of focal necrotic lesions with a predilection for the basis pontis and a clinical deficit inconsistent with survival past 6 months. Accumulation of minute mineral deposits and atherosclerotic plaques were also noted in these monkeys and appeared to be related to both dose and survival time.

Animals↗

[Hereditary melanotic tumors of Drosophila. Determination of the tumorous transformation of larva hemocytes].

Two different phenomena contribute to the histogenesis of melanotic formations in tumoral strains of drosophila : an abnormal multiplication of certain blood cells and their encapsulation by normal hemocytes. The statistical distribution of melanotic tumors in populations of individuals submitted during precise periods of their life to the action of agents such as supraoptimal temperature or ionizing radiations, permits to suggest for the tumoral transformation of larval hemocytes in drosophila, the following mechanism : this transformation is caused by an event occuring in the cytoplasm and determined by the activity of a nuclear gene.

Animals↗