125Iodine decay in DNA: A discussion of its effectiveness for the breaking of DNA strands

Summary ¹²⁵I incorporated in DNA is known to be exceptionally toxic. Values of D₀ range from about 40 to about 90 decays for survival of mammalian cells. The effectiveness of¹²⁵I in DNA with respect to the induction of breaks of the DNA strands, however, appears to be comparatively low. The numbers of strand breaks per energy deposited in subnuclear cellular structures such as DNA is smaller for a disintegration of¹²⁵I than for-rays. The difference in effectiveness diminishes with increasing mass of the considered sensitive volume. The apparent inefficiency of¹²⁵I-decay may, on one hand, result from a waste of local energy deposition. On the other hand, it may be caused by a multitude of local strand breaks (clusters) induced by¹²⁵I-decay which are measured as one break only by the conventionally applied techniques of strand break measurement. The apparent inefficiency of¹²⁵I may be evidence furthermore for the importance of considering not only the DNA as the sensitive target but with equal pertinence the gross sensitive volume, i.e. the whole cell nucleus [12]. Further, for drawing meaningful comparisons, it may be necessary to take into consideration the microdosimetric event size distributions for the critical targets [1].Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

A quantitative method for assessing stages of the rat estrous cycle

The impact of gender and/or hormone variations on a wide variety of neural functions makes the choice between studying males or females (or both) of a given species difficult. Although female rats are widely used experimentally, few studies control for the stage of estrus. More detailed information about how to distinguish the various stages of the estrous cycle is needed. For the present study, vaginal smears were obtained once a day and stained using an adaptation of the Papanicolaou (PAP) procedure. Images are provided of unstained “wet” samples and the corresponding PAP stained smears illustrating the cellular profile for each stage of the cycle as well as post-ovariectomy. The different cell populations across the cycle were quantified and ratios determined to show trends between the predominant and other cell types in each stage of the estrous cycle. Both stained and unstained images and cell quantification data provide valuable guidelines for distinguishing the stages of the estrous cycle.     

Weight loss is not mandatory for exercise-induced effects on health indices in females with metabolic syndrome

The aim of this study was to investigate the impact of moderate aerobic training on functional, anthropometric, biochemical, and health-related quality of life (HRQOL) parameters on women with metabolic syndrome (MS). Fifteen untrained women with MS performed moderate aerobic training for 15 weeks, without modifications of dietary behaviours. Functional, anthropometric, biochemical, control diet record and HRQOL parameters were assessed before and after the training. Despite body weight maintenance, the patients presented decreases in waist circumference (P = 0.001), number of MS components (P = 0.014), total cholesterol (P = 0.049), HDL cholesterol (P = 0.004), LDL cholesterol (P = 0.027), myeloperoxidase activity (P = 0.002) and thiobarbituric acid-reactive substances levels (P = 0.006). There were no differences in total energy, carbohydrate, protein and lipid intake pre- and post-training. Furthermore, improvements in the HRQOL subscales of physical functioning (P = 0.03), role-physical (P = 0.039), bodily pain (P = 0.048), general health (P = 0.046) and social functioning scoring (P = 0.011) were reported. Despite the absence of weight loss, aerobic training induced beneficial effects on functional, anthropometric, biochemical and HRQOL parameters in women with MS.     

A microdosimetric interpretation of the radiobiological effectiveness of125I and the problem of quality factor

Summary When considering the microdosimetric energy deposition in small biological targets the Auger electron emitter¹²⁵I behaves like a high-LET radiation. For a specific incorporation in sensitive biological volumes of 20 nm in diameter a mean lineal energy of keV µm^–1 has been evaluated. Experimental data on transformation, mutation and chromosome aberration from DNA-bound¹²⁵I are interpreted to yield RBE-values, relative to 200 kV X rays, of 32 to 38 (transformations), 1 to 16 (mutations) and 6 to 77 (chromosome aberrations). Thus the RBE for transformation and chromosome aberration tends to be larger than the ICRP recommended high-LET quality factor (Q=20). The implications of these results for the functionQ(L) applied in radiation protection will be discussed.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

5-Fluorouracil treatment after irradiation impairs recovery of bone marrow functions

Summary In mice, persisting radiation-induced growth retardation of hematopoietic tissue suggested that at least part of the surviving stem cells are genetically injured. Additional mitotic stress some time after the radiation insult might remove injured stem cells, thus improving the overall recovery of the irradiated bone marrow.Mice were treated with 5 Gy whole-body gamma irradiation. Two weeks later half of the animals were injected i.v. with 150 mg/kg 5-fluorouracil (5-FU), the other half remained untreated (5 Gy-controls). 2 or 10 weeks later, femoral cellularity and CFU-S content, proliferation ability of transplanted bone marrow and the compartment ratio (CR; ratio of splenic IUdR incorporation at day 3 and number of CFU-S transfused) were determined.Four weeks after 5 Gy and 2 weeks after 5-FU treatment all parameters showed significant impairment of recovery. 12 weeks after 5 Gy and 10 weeks after 5-FU CFU-S and CR were still reduced compared to the 5 Gy-controls. 5-FU treatment of unirradiated mice did not produce permanent effects on the quality of stem cells or the hematopoietic microenvironment. It is concluded, therefore, that an increased proliferation stimulus does not aid in the removal of injured CFU-S and may even impair recovery of bone marrow functions by increasing the proportion of genetically injured stem cells which continue proliferation.Dedicated to Prof. L.E. Feinendegen on the occasion of his 60th birthday     

In vivo enzyme control through a strong stationary magnetic field--the case of thymidine kinase in mouse bone marrow cells

The influence of a strong homogeneous and stationary magnetic field (SMF) on the activity of the enzyme thymidine kinase (TdR-K) in bone marrow cells, and as a consequence of this on the incorporation of 125I-labelled 5-iodo-2-deoxyuridine (125IUdR) into DNA of mice and into isolated bone marrow cells in vitro, was assayed after exposure of immobilized mice. No effect could be elicited in moving mice, in cells in suspension or in enzyme in solution. The response depended on the body temperature during exposure: at 27 degrees C and 29 degrees C there was an increase and at 37 degrees C and a depression of enzyme activity. The TdR-K activity at low temperature increased with the field strength ranging from 0.2 to 1.4T. Thirty minutes were required for full expression of the effect at 1.4T; 5-10 min were needed after exposure for a return to base-line levels. Mice were given total-body irradiation at a dose of 0.1 Gy 137Cs gamma rays and then exposed immediately to a magnetic field at 1.4T for 30 min at a body temperature of 27 degrees C; gamma irradiation no longer inhibited the enzyme. Exposure to the magnetic field further removed from the time of gamma irradiation, did not negate the inhibitory effect of gamma irradiation. The observed responses to given challenges in this complex system support the hypothesis that the magnetic field affects TdR-K activity by way of a mediating structure, such as a membrane.     

Study of cell death in Friend leukaemia.

Cell death of splenic Friend leukaemic cells has been studied in vivo, using 125I-UdR and 3H-TdR pulse labelling. The evolution of the splenic specific activity has been measured by autoradiography and external counting during 40 hr after injection of the labelled precursor. These two techniques show the existence of a large reutilization of 3H-TdR (50%), which is measurable as soon as 7 hr after the injection. The DNA turnover rate is rapid, 83-8% of the splenic cellular DNA being renewed per day. Those results confirm that most of the cells produced in the Friend leukaemic spleen are rapidly lost; they also demonstrate that this cell loss is mainly due to a massive death, which occurs in proerythroblastic and erythroblastic compartments after one or two cell divisions. Friend leukaemic cells, which are characterized by a limited capacity of proliferation and a short lifespan, do not appear to be malignant.