The blood spot thyrotropin method is not adequate to screen for hypothyroidism in the elderly living in abundant-iodine intake areas: comparison to sensitive thyrotropin measurements.

We investigated whether the blood spot thyrotropin (TSH) method was adequate for screening elderly subjects with abundant iodine intake (median excretion 330 microg/g creatinine) for hypothyroidism. In 97 healthy adults (group A), 210 nursing home residents (group B) and 265 elderly subjects living at home (group C) serum (sensitivity < 0.02 mU/L, cost 1.2 U.S. dollars [USD]) and blood spot TSH (sensitivity < 1.0 mU/L, cost 0.4 USD) were measured, and the sensitivity and specificity of different blood spot TSH cutoff points to detect cases with elevated serum TSH were calculated. Elevated (> 3.5 mU/L) serum TSH levels (group A, 6.2%; group B, 16.2%; group C, 22.3%; B > A, p = 0.025; C > A, p < 0.001) were detected with the required sensitivity of greater than 0.9 only if the cutoff point of the blood spot TSH was set as low as 2.5 mU/L, but this led to a considerable loss of specificity. At cutoff point 2.5 mU/L, the rate of positivity was 39.3% and the cost of blood spot screening/person increased to 0.88 USD, considering that positive cases have to be rechecked by serum TSH to exclude false positivity. Cases with significantly elevated (> 10.0 mU/L) serum TSH (group A, 1.03%; group B, 2.85%; group C, 2.20%) were detected at blood spot cutoff points 10.0-4.0 mU/L with a sensitivity of 1.0 and without considerable loss of specificity. We conclude that while screening for hypothyroidism in the elderly population with abundant iodine intake is justified by the high prevalence of elevated ultrasensitive serum TSH values, the sensitivity of the blood spot method is insufficient to detect the subclinical hypothyroidism accurately and would, therefore, fail to detect most affected subjects.

Thermal sensitivity and radiosensitization in Chinese hamster V79 cells exposed to 2-aminopurine or 6-thioguanine.

Chinese hamster V79 cells were exposed to 10(-6) mol liter-1 2-aminopurine (2-AP) or 6-thioguanine (6-TG) for 18 or 40 h, and then tested for sensitivity to X rays, heat, or a combined treatment of heat and radiation. Cells exposed to 6-TG were sensitive to X rays, while those treated with 2-AP showed little or no sensitivity. At 42 degrees and 45 degrees C moderate sensitization resulted from 2-AP treatment, with greater sensitization resulting from treatment with 6-TG. Combined heat and X-ray treatment of cells exposed to 2-AP yielded sensitization similar to heat treatment alone, while cells exposed to 6-TG before receiving the combined treatment showed a degree of sensitization greater than that due to either treatment by itself but less than that of the two treatments added together. Uptake of the purine analogues into cellular DNA was measured by high-pressure liquid chromatography. At the 1% detection level, after either an 18- or a 40-h exposure of cells to 10(-6) mol liter-1 2-AP or 6-TG, no base substitution was found. Analysis of cell cycle distributions by flow cytometry revealed only very small changes following exposure of cells to the purine analogues.

A study of heat and radiation response of a malignant, melanin-producing cell line derived from C3H 10T1/2 cells transformed in culture by radiation.

The mouse C3H 10T1/2 cell line was transformed to the malignant state using ionizing radiation. One of the transformed lines (R25) that was isolated, displayed some properties similar to malignant melanoma cells. The cells became dark and pigmented after prolonged time in culture and this cell line produced tumors in C3H mice. The radiation survival curve of R25 had a large shoulder which was also observed for human melanoma cell lines. R25 was more resistant to heating at 45.0 degrees C than the normal cell line. Heating at 45.0 degrees C before irradiation resulted in a reduction of the survival curve shoulder. The heat and radiation sensitivity of R25 did not appear to be related to the melanin content of these cells.

Comparison of heat and/or radiation sensitivity and membrane composition of seven X-ray-transformed C3H 10T1/2 cell lines and normal C3H 10T1/2 cells.

C3H 10T1/2 mouse embryo cells were transformed by X-irradiation, and seven transformed clones were isolated and propagated as cell lines. Some of these cell lines produced tumors in syngeneic mice and grew in agarose while the normal C3H 10T1/2 cell line did not possess these characteristics. Exponentially growing cell cultures with comparable cell-cycle distributions as measured by flow cytometry were tested for heat and X-ray sensitivity. The heat and X-ray sensitivity varied randomly compared to the normal cell line. One cell line was more heat resistant and one more heat sensitive than the normal cell line, and the others had sensitivities comparable to the normal cell line. Measurements on some of the biochemical parameters of the particulate fraction of cells after sonication and 24,000 X g centrifugation showed that altered thermal sensitivity was not correlated with protein, cholesterol, or phospholipid content of this fraction.

Ataxia telangiectasia cells exhibit the same radiosensitization response by incorporation of BrdUrd or IdUrd as do normal human cells.

Normal and ataxia telangiectasia (AT) human cells were exposed to 10(-5) mole/liter bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd). High-pressure liquid chromatography (HPLC) measurements showed that up to 26 and 23% of the thymidine in DNA was substituted by BrdUrd in normal and AT cells, respectively. The incorporation of BrdUrd or IdUrd into DNA resulted in radiosensitization in normal and AT cells. When exposed to equal concentrations of BrdUrd and IdUrd, the BrdUrd caused greater radiosensitization than IdUrd in both normal and AT cells.

Growth of a radiation-transformed clone of C3H 1OT1/2 cells into melanin-producing colonies.

When R25, a radiation-transformed clone of C3H 1OT1/2 cells, was plated in soft agarose, a fraction of the colonies became pigmented. The morphologies of the white and dark colonies and their cells were compared by optical, transmission and scanning electron microscopy. The transformed R25 cells had apparently differentiated into melanin-producing cells in the soft agarose, with the white colonies containing actively growing cells having only a few melanosomes, and the dark colonies being made up of stationary-phase cells filled with electronopaque melanosomes. Exposure of the R25 cells to 4.0 Gy of X-rays decreased the percentage of dark colonies, while exposure to 1% DMSO had no effect.

Inhibition of DMSO-induced differentiation by hyperthermia in a murine erythroleukemia cell system.

Friend erythroleukemia cells were induced by dimethyl sulfoxide (DMSO) into erythroid differentiation, as characterized by the production of hemoglobin. Induction increased with DMSO concentrations up to 1.5% v/v, at which point about 90% of the cell population produced hemoglobin as measured by a benzidine-staining technique. Heat treatment at 39.0-40.5 degrees C during a 7-day-incubation period, for differentiation in the presence of DMSO, resulted in the inhibition of hemoglobin induction. Also, acute heat treatments at 41.5-46.0 degrees C before or after the addition of DMSO resulted in the inhibition of DMSO induction. This effect was greatest when DMSO was present during heating. The results support the conclusion that hyperthermia inhibits the differentiation process which is induced by DMSO treatment.

Thermal sensitivity and radiosensitization in V79 cells after BrdUrd or IdUrd incorporation.

Chinese hamster V79 cells were exposed to 10(-5) moles/liter bromodeoxyuridine (BrdUrd) or iododeoxyuridine (IdUrd) for 16 or 29 hr and then tested for thermal sensitivity, radiosensitivity, and sensitivity to the combined treatments of heat and radiation. BrdUrd and IdUrd treatment of cells resulted in enhanced radiosensitivity which increased with exposure time but had little or no effect on thermal sensitivity. For 42.0 degrees C heating, no effect was observed, while for 45.0 degrees C heating, a small decrease in thermal sensitivity occurred for both 16- and 29-hr exposure times, in the combined treatment of heat and radiation, the presence of BrdUrd or IdUrd resulted in about the same thermal enhancement in radiosensitivity. BrdUrd and IdUrd uptake into cellular DNA were measured using high-pressure liquid chromatography and, after a 29-hr exposure to 10(-5) moles/liter of BrdUrd or IdUrd, approximately 40% of the thymidine was substituted.

Effect of gamma radiation on E. coli ribosomes. I. Inactivation by hydrogen atoms, hydroxyl radicals, hydrated electrons and secondary radicals.

E. coli ribosomes in aerated solutions were inactivated with a D37 dose of 144 Gy. In comparison, deaerated solutions bubbled with N2 or N2O showed a slight enhancement of the inactivation with D37 doses of 115 and 125 Gy, respectively. Isopropanol and tertiary-butanol provided partial protection. Results show that hydroxyl radicals, hydrated electrons and hydrogen atoms are involved in the inactivation process. Secondary radicals derived from the alcohols also inactivate ribosomes, with reduced efficiency.

Hyperthermia in a differentiating murine erythroleukaemia cell line: II. Effect of heat on haem induction by radiation.

Friend erythroleukaemia cells (FELC) were induced to a haem-producing state by X-rays. The percentage of haem positive cells was maximum for doses between 10 and 15 Gy. Heat treatment at 42.0 degrees C or 45.0 degrees C during or after irradiation inhibited haem induction whereas heating before irradiation enhanced it. Incubation at 37 degrees C between heating and irradiation resulted in a decline in induction levels, indicating repair of heat damage that interacts with X-ray damage. Incubation at 37 degrees C between irradiation and heating did not result in changed haem induction levels, indicating a lack of repair of radiation damage that could interact with subsequent damage produced by heating.

Effect of gamma radiation on E. coli ribosomes, tRNA and aminoacyl-tRNA synthetases.

Gamma-irradiated E coli ribosomes and tRNA, in aerated solutions, were inactivated with D37 doses of 144 and 77 Gy, respectively. Aminoacyl-tRNA-synthetases were only slightly inactivated under comparable conditions. Effects of additives to ribosome and tRNA solutions suggest that hydroxyl radicals were the major damaging species, that superoxide anions were not damaging and that radiolytically-formed hydrogen peroxide was also unimportant. Part of the damage by hydroxyl radicals is expressed through secondary radicals produced from additives and buffers. Results obtained with three different buffers suggest that (1) acetate ions provide protection by competing for hydroxyl radicals, (2) chloride ions are without effect and (3) inactivation of ribosomes and aminoacyl-tRNA-synthetases in Tris-HCl/MgCl2 and phosphate/MgCl2 buffered solutions was similar but the tRNA inactivation was lower in Tris-HCl/MgCl2 buffer.