phosphorus-radioisotopes and Leukemia--Radiation-Induced

By definition, idiopathic erythrocytosis (IE) applies to a group of patients characterised by having a measured RCM above their predicted normal range (an absolute erythrocytosis) and following investigation do not have a form of primary or secondary erythrocytosis. Patients with IE are heterogenous. The possibilities include physiological variation, 'early' polycythaemia vera (10-15% develop clear features of PV over a few years), unrecognized congenital erythrocytosis, unrecognized or unrecognizable secondary acquired erythrocytosis or a currently undescribed form of primary or secondary erythrocytosis. Patients are more commonly male with a median age at presentation of 55-60 years. Approximately half of the patients present with vascular occlusive complications. Retrospective evidence indicates that vascular occlusion occurs less frequently when the PCV is controlled at normal levels. Venesection is the treatment of choice to lower the PCV. As a general approach to management, all patients with a PCV above 0.54 should be venesected to a PCV less than 0.45. This target PCV should also apply to patients with lesser degrees of raised PCV who have additional other risk factors for vascular occlusion.

Topics: Aged; Arterial Occlusive Diseases; Bone Marrow; Chlorambucil; Diagnosis, Differential; Endocrine System Diseases; Erythrocyte Volume; Erythroid Precursor Cells; Erythropoietin; Genetic Predisposition to Disease; Humans; Hypoxia; Kidney Diseases; Leukemia; Leukemia, Radiation-Induced; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Polycythemia Vera; Receptors, Erythropoietin; Sequence Deletion; Smoking; Stroke

The clinical course in both polycythaemia vera (PV) and essential thrombocythaemia (ET) is characterized by significant thrombohaemorrhagic complications and variable risk of disease transformation into myeloid metaplasia with myelofibrosis or acute myeloid leukaemia. Randomized studies have shown that the risk of thrombosis was significantly reduced in ET with the use of hydroxyurea (HU) and in PV with the use of chlorambucil or 32P. However, the use of chlorambucil or 32P has been associated with an increased risk of leukaemic transformation. Subsequently, other studies have suggested that both HU and pipobroman may be less leukaemogenic and as effective as chlorambucil and 32P for preventing thrombosis in PV. However, the results from these prospective studies have raised concern that even HU and pipobroman may be associated with excess leukaemic events in both ET and PV. The recent introduction of anagrelide as a specific platelet-lowering agent, the demonstration of treatment efficacy with interferon-alpha, and the revived interest in using low-dose acetylsalicylic acid provide the opportunity to initiate prospective randomized studies incorporating these treatments.

Topics: Adult; Aged; Aspirin; Chlorambucil; Disease Progression; Female; Hemorrhage; Humans; Hydroxyurea; Interferon-alpha; Leukemia, Myeloid; Leukemia, Radiation-Induced; Male; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Primary Myelofibrosis; Prospective Studies; Quinazolines; Thrombocythemia, Essential; Thrombosis

Topics: Acute Disease; Alkylating Agents; Busulfan; Chlorambucil; Humans; Hydroxyurea; Leukemia, Myeloid; Leukemia, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Platelet Aggregation Inhibitors; Polycythemia Vera; Randomized Controlled Trials as Topic; Survival Rate

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

The treatment of polycythemia vera with 32phosphorus (32P) raises two problems: 1) what is its therapeutic efficacity? 2) Does the use of 32P increase the risk of acute leukemia? The large series of treated patients have shown the remarkable efficacy of 32P. This is particularly evident when comparing the recent series of patients treated with 32P with those of Videbaek whose patients were treated by phlebotomies only. Patients are treated one time with 3.7 x 10(6) mBq (0.1 mCi) of 33P per kg of body weight. Granulocytes and platelets are rapidly affected, whereas red cells show a response 3 months later due to their longer survival. Remission lasts from a few months to three years. If the result is not satisfactory, another dose can be given 3 months after the first one. Resistance to 32P may arise but may be reversible after a course of chemotherapy. The clear therapeutic effect of 32P renders it especially valuable for patients with a high vascular risk. Some authors have claimed that polycythemia vera evolves towards acute leukemia, but Modan's study has demonstrated that 32P is indeed responsible for the occurrence of acute leukemia; this has been largely confirmed by others. The dose to the bone marrow is not negligible and the leukemic incidence following the treatment is a factor which limits its indication. Trials were conducted to search for therapies with alkylating agents, such as Chlorambucil or Busulphan, which would be less leukemogenic. The Polycythemia Vera Study Group found that Chlorambucil was at least 2.3 fold more leukemogenic than 32P. The EORTC compared the leukemogenic effect of 32P with that of Busulphan.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Cell Division; Humans; Leukemia, Radiation-Induced; Phosphorus Radioisotopes; Polycythemia Vera; Risk Factors

Virtually every aspect concerning the occurrence of acute leukemia in polycythemia vera is controversial. However, a list of those factors believed to have importance in leukemogenesis in this disease includes: maleness, ethnic origin, the presence of myeloid metaplasia and/or early WBC precursors in the peripheral blood at the time of presentation, the influence of prolonged survival, and a possible dose-response relationship with 32P treatment. Many of the features of PV suggest that it is a malignant disease per se, with other factors (such as clones of cells, or altered host response) combining to increase the leukemogenic potential of the agents used to control the disease. It does appear that the incidence of AL in PV treated with 32P and/or x-ray is many times higher than that for PV treated with phlebotomy alone. However, overall survival for 32P-treated patients appears to be longer than that for phlebotomy treatment. Further, for both 32P and phlebotomy treatments, patients with AL do not die an an earlier age than do patients not developing this complication. Since the transformation of PV into AL has been described in more than 20 patients treated with phlebotomy alone, and in more than 30 patients treated with chemotherapy and phlebotomy, the question concerning the occurrence of AL in PV no longer appears to revolve around whether this is a function of the leukemogenicity of 32P or the effect of prolongation of survival. The occurrence of AL in multiple myeloma, lymphomas, other malignancies, and in nonmalignant diseases following treatment with myelosuppressive agents, forces one to consider the leukemogenic potential of any agent capable of suppressing the panmyelopathy of this disease, as well as the inherent tendency to AL of the "untreated" disease. Hopefully, the next decade will give us a more complete understanding of the complex interrelationships between PV, its treatment, and AL.

Topics: Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Radiotherapy; Sex Factors

Topics: Hemorrhagic Disorders; Humans; Leukemia, Radiation-Induced; Leukopenia; Methods; Osteosclerosis; Phosphorus Radioisotopes; Polycythemia Vera; Prognosis; Radiotherapy; Radiotherapy Dosage; Remission, Spontaneous; Thrombocytopenia; Time Factors

Topics: Bone Neoplasms; Contrast Media; Germany; Humans; Iodine Radioisotopes; Leukemia, Radiation-Induced; Liver Neoplasms; Lung Neoplasms; Mining; Neoplasms, Radiation-Induced; Pacific Islands; Paranasal Sinus Neoplasms; Phosphorus Radioisotopes; Polycythemia Vera; Radioactive Fallout; Radiotherapy; Radium; Radon; Spondylitis, Ankylosing; Thorium; Thorium Dioxide; Thyroid Neoplasms; United States; Uranium

Despite myelosuppression, polycythemic (PV) patients greater than 65 years of age have a high risk of vascular complications, and the leukemic risk exceeds 15% after 12 years. Is the addition of low-dose maintenance treatment with hydroxyurea (HU) after radiophosphorus (32P) myelosuppression able to decrease these complications? Since the end of 1979, 461 patients were randomized to receive (or not) low-dose HU (5 to 10 mg/kg/d), after the first 32P-induced remission, and were observed until death or June 1996. Maintenance treatment very significantly prolonged the duration of 32P-induced remissions and reduced the annual mean dose received to one-third. However, despite this maintenance, 25% of the patients had an excessive platelet count and the rate of serious vascular complications was not decreased, except in the most severe cases with short-term relapse of polycythemia. Furthermore, the leukemia rate was significantly increased beyond 8 years and a significant excess of carcinomas was also observed. The continuous use of HU did not decrease the risk of progression to myelofibrosis (incidence of 20% after 15 years). Life expectancy was shorter (a median of 9.3 years v 10.9 years with 32P alone), except in the most severe cases (initial 32P-induced remission lasting <2 years) in which maintenance treatment moderately prolonged the survival by reducing the vascular risk. In most cases of PV, in which the duration of the first 32P-induced remission exceeded 2 years, the introduction of HU maintenance did not reduce the vascular risk. Although it considerably decreased the mean dose of 32P received, HU maintenance therapy significantly increased the leukemia and cancer risks and reduced the mean life expectancy by 15%. However, in cases with more rapid recurrence, the introduction of maintenance treatment reduced the vascular risks and moderately prolonged survival. The use of HU as a maintenance therapy is therefore only justified in this situation.

Topics: Actuarial Analysis; Aged; Alkylating Agents; Combined Modality Therapy; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis; Risk; Survival Analysis; Vascular Diseases

An analysis of the risk of progression towards leukemia, carcinoma and myelofibrosis was performed in 93 patients treated by 32P alone (PVSG protocols) since 1970-1979, 395 patients over the age of 65 years treated by 32P with or without maintenance therapy using hydroxyurea (French protocol) since 1980-1994, and 202 patients under the age of 65 treated by either hydroxyurea or pipobroman since 1980. The risk of leukemia, or myelodysplasia, or lymphoma in the 32P-treated patients was 10% at the 10th year, but increase after that time to reach a value of about 30% at the 20th year, in the surviving case. This risk was not dose-related. Despite a marked reduction of the cumulative 32P dose in the patients maintained by hydroxyurea, the actuarial risk was 19% at the 10th year. In the patients treated exclusively by non radio-mimetic agents (hydroxyurea or pipobroman) a risk of 10% at the 10th year was observed. The risk of carcinoma (excluding skin cancers) was about 15% at the 10th year in the 32P-treated cases, a value similar to that generally reported by the French statistics. There was no prevalence of digestive carcinomas. In contrast, the patients receiving 32P and hydroxyurea as maintenance had an excess risk: 29% at the 10th year. In the relatively young cases treated by non radio-mimetic agents, the risk was similar in both arms: 9% at the 10th year, similar to the expected incidence at this age. The risk of myelofibrosis with myeloid metaplasia was still relatively low at the 10th year, about 15% in all arms, but increased towards a value higher than 30% in the patients surviving at the 20th year. At the present time, but in only a few cases with long-term following, no myelo-fibrosis with splenic metaplasia has been observed in the pipobroman-treated cases. The present results, which need to be confirmed (the present analysis has been done in spring 95) suggest that:-the use of non radio-mimetic agents does not protect against leukemic transformation, which may be a consequence of the disease; rather than of the treatment,-maintenance therapy after initial use of 32P increases the risk of both leukemia and carcinoma,-and hydroxyurea does not delay the risk of developing myelo-fibrosis, in comparison with 32P alone.

Topics: Actuarial Analysis; Acute Disease; Carcinoma; Cause of Death; Disease Progression; Follow-Up Studies; Humans; Hydroxyurea; Incidence; Leukemia, Myeloid; Leukemia, Radiation-Induced; Lymphoma; Neoplasms, Radiation-Induced; Phlebotomy; Phosphorus Radioisotopes; Pipobroman; Polycythemia Vera; Prevalence; Primary Myelofibrosis; Risk; Splenomegaly

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Topics: Acute Disease; Anemia, Refractory, with Excess of Blasts; Busulfan; Cell Transformation, Neoplastic; Chlorambucil; Cohort Studies; Disease Progression; Drug Therapy, Combination; Enzyme Inhibitors; Female; Humans; Hydroxyurea; Incidence; Interferon-alpha; Leukemia; Leukemia, Radiation-Induced; Male; Melphalan; Middle Aged; Phlebotomy; Phosphorus Radioisotopes; Polycythemia Vera; Preleukemia; Primary Myelofibrosis; Retrospective Studies; Ribonucleotide Reductases; Risk; Thrombocythemia, Essential

For 366 patients with polycythaemia vera (PV) or essential thrombocythaemia (ET) diagnosed 1971-1990, oral administration of 32-P was used as myelosuppressive treatment. Retreatment was not restricted to any defined interval and the number of treatments or the total dose were not limited. For 107 patients, follow-up was > 10 years. 15 of these presented with life-threatening occlusive vascular symptoms and their survival was short. For the remaining 92 patients 5-yr survival was not significantly worse than for a Swedish population matched for age and sex. Survival at 10 yr was lower, 51% versus 66% expected. Acute myeloid leukaemia (AML) was diagnosed in 11 of the 107 patients (10.3%). In the whole material of 366 patients, 17 have developed AML with a median time of 8.5 yr from start of treatment. There was a maximum incidence of 4% per yr after 8-12 yr. Later, the incidence decreased. The median annual dose of 32-P for the AML patients was 100 MBq and was not significantly larger than for a matched control group surviving without AML, 96 MBq. The results are compared with reports on PV or ET patients treated with busulphan (Bu) or hydroxyurea (HU). With comparable periods of follow-up there are no indications that an adequate myelosuppression with oral 32-P will be associated with shorter survival or higher incidence of AML than treatment with Bu or HU. It is concluded that, for the time being, oral administration of 32-P is an acceptable standard treatment in PV and ET.

Topics: Administration, Oral; Aged; Busulfan; Female; Humans; Hydroxyurea; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Neoplasms, Second Primary; Phosphorus Radioisotopes; Polycythemia Vera; Thrombocytosis; Time Factors

The fate of the polycythaemic patient depends on the treatment employed which may determine the nature of the transformation commonly occurring late in the course of the disease. Treatment is, on the other hand, aimed at prevention of the most frequent complications, that is of thromboembolic processes. In the last 30 years the authors treated a total of 118 PV patients, of whom 60 have died. Initially 32P treatment was applied, which was modified later, because of acute leukaemia that had occurred in 9% of the treated cases, to a single 5 mC 32P+Myelobromol (DBM) treatment. Still later only DBM was administered in the form of stosstherapy (2500 mg per day over a period of 4 days). In the latter two groups, acute leukaemia occurred as few as two cases. The course of untreated polycythaemia vera is characterized by transformation into another myeloproliferative disease. This phenomenon occurs in 50% of the cases on drastic treatment and in patients treated with 32P. Of the patients who were alive when the report was finished 35% had been free of complications, while 5.2% were suffering from chronic granulocytic leukaemia (CGL), 34.5% from sclerotic osteo-myelofibrosis (OMF-SC) and 3.4% from chronic megakaryocytic granulocytiv leukaemia (CMGL). Of the 60 patients having died, 15% had suffered from other complications being predominantly of vascular nature. 11.8% of them died of AML, 10% of CGL, 26.7% of OMF-SC and 26.7% of CMGL. The terminal stage was characterized, in the majority of cases, by blastic crisis. Based on their own results and literary data authors recommend DBM treatment besides the indispensable phlebotomy.

Topics: Adult; Aged; Aged, 80 and over; Chlorambucil; Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Middle Aged; Mitobronitol; Phosphorus Radioisotopes; Polycythemia Vera; Primary Myelofibrosis

The therapeutic approach of internally administered radiopharmaceuticals offers the potential to outmode the present approaches of conventional radiation therapy and chemotherapy because of three characteristics: 1. The therapeutic use of radiopharmaceuticals may deliver as much as orders of magnitude larger rad doses than conventional radiation therapy to target tissues, selectively irradiating these tissues internally in one radiation dose. 2. The therapeutic use of radiopharmaceuticals is followed by a lower incidence of leukemia and other cancers. 3. The treatment is comparatively noninvasive and nontraumatic. We can now make this rather strong statement with fairly firm conviction because Na131I has been used since 1946 (33 years) to treat almost a million patients for hyperthyroidism (a) and in approximately 5000 patients for well-differentiated thyroid cancer (b); NaH2PO4(P-32) has been used for 35 years to treat approximately 25,000 patients with polycythemia vera (3-5).

Topics: Forecasting; Humans; Hyperthyroidism; Iodine Radioisotopes; Leukemia, Radiation-Induced; Neoplasms, Radiation-Induced; Phosphates; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Radiotherapy Dosage; Sodium Iodide; Thyroid Neoplasms

Topics: Acute Disease; Adult; Aged; Bloodletting; Busulfan; Evaluation Studies as Topic; Female; Humans; Leukemia; Leukemia, Radiation-Induced; Male; Mercaptopurine; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Thromboembolism; Veins

In 1954 a then 31-yr-old male was found to have erythrocytosis. Over the ensuing decade he received 72 mCi32P. In 1964 his daughters were found to have erythrocytosis. Further investigation led to the discovery of hemoglobin Yakima, a variant with high oxygen affinity. He received no further therapy and was well until 1975, when he developed the preleukemic syndrome. Within 12 mo. he developed acute nonlymphocytic leukemia accompanied by fetal erythropoiesis. Because the inital discovery of this type of hemoglobinopathy came 27 yr after the introduction of 32P for use in the treatment of polycythemia vera, and because there are now known to be more than 39 different high-oxygen-affinity hemoglobins, we anticipate that more patients such as ours have been exposed to 32P. The exposed population should be cosely followed, since this will likely permit assessment of the risk of 32P-induced leukemia in a nonneoplastic condition.

Topics: Acute Disease; Adult; Erythropoiesis; Hemoglobins, Abnormal; Humans; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia; Preleukemia; Time Factors

Topics: Aged; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera

Results are presented of chromosome studies of bone marrow cells from a 62-year-old woman. The patient had been given 40 ml of Thorotrast in connection with a neuro-radiological examination 34 years earlier. Clinically, the patient was now considered to be in an incipient myeloid leucaemic phase. Ninety-seven per cent of the bone marrow cells belonged to a clone with characteristic marker chromosomes induced by radiation. Few data are available on chromosome analysis of bone marrow cells from Thorotrast patients. Therefore, the results of the present study are compared with data from chromosome analyses of 32P-treated patients with polycythaemia vera, in whom large clones were found in the bone marrow. The results of chromosome analysis of bone marrow cells from the Thorotrast patient support previous hypotheses concerning the carcinogenesis in radiation-induced leucaemia in patients with polycythaemia vera, treated with 32P. In the latter patients, the clone cells are pressumed to represent cell populations with selective qualities, originating from radiation-damaged cells, which possibly possess an increased tendency to malignant transformation because of a more pronounced sensitivity to carcinogenic agents. The cells might also be potentially malignant and manifest themselves as leucaemic cells, if the patient's immunological defence mechanism is broken.

Topics: Bone Marrow; Bone Marrow Cells; Chromosome Aberrations; Chromosome Inversion; Chromosomes, Human, 1-3; Clone Cells; Female; Humans; Karyotyping; Leukemia, Myeloid; Leukemia, Radiation-Induced; Middle Aged; Phosphorus Radioisotopes; Radiation Effects; Thorium Dioxide

Topics: Child, Preschool; Humans; Japan; Leukemia, Radiation-Induced; Lung Neoplasms; Neoplasms, Radiation-Induced; Nuclear Warfare; Phosphorus Radioisotopes; Radium; Skin Neoplasms; Thorium Dioxide; Thyroid Neoplasms

Topics: Adult; Aged; Female; Humans; Leukemia, Radiation-Induced; Male; Middle Aged; Phosphorus Radioisotopes; Polycythemia Vera; Radiotherapy; Radiotherapy Dosage

Topics: Humans; Leukemia; Leukemia, Radiation-Induced; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity