DNA repair capacity measured by high throughput alkaline comet assays in EBV-transformed cell lines and peripheral blood cells from cancer patients and healthy volunteers.

We collected peripheral blood (PB) from 556 patients with various types of cancer who had undergone radiotherapy and from 81 healthy volunteers. We exposed whole PB and Epstein-Barr virus-transformed lymphoblastoid cell lines (EBLs) derived from the PB mononucleocytes to X-irradiation (5 Gy). Using the alkaline comet assay, we measured the immediate DNA damage and, at 15 min, the % residual damage. In PB, the immediate damage was similar in patients and healthy volunteers while the % residual damage (mean+/-S.D.) was significantly higher in patients with breast (54.3+/-A23.9), cervical (54.7+/-A23.9), head/neck (56.8+/-A24.4), lung (60.1+/-23.5), or esophageal cancers (59.5+/-A33.7) than in healthy donors (42.9+/-19.6) (P<0.05). We did not observe such differences in the EBV-transformed cell lines. Thus, radiation sensitivity of fresh PB cells measured by the alkaline comet assay was related to cancer status.

Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor.

We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer, with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6+/-3.8 to 36.3+/-14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8+/-6.8 to 70.5+/-10.5 days and 70.7+/-1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4+/-18 to 62.6+/-9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets for manipulation of radiosensitivity, and that induction of an alternative pathway may enhance radiosensitivity of pancreatic cancer.

Fractionated irradiation augments inter-strain variation of skin reactions among three strains of mice.

The multifraction regimens commonly used in conventional clinical radiotherapy are largely based on radiobiological experiments. However, no experimental reports on skin reactions focusing on inter-strain differences have displayed clinical relevance to the fractionated dose schedule. In this study, mice of inbred strains A/J, C57BL/6J, and C3H/HeMs were used to reveal inter-strain difference after multifractionated irradiation. Irradiation was performed daily at graded doses of 30-60 Gy total doses, with 10 fractions of 3-6 Gy. Acute skin reactions following irradiation were scored for 50 days after irradiation. Dividing a dose into a number of fractions obviously spared skin damage in the three strains of mice. No mouse exhibited a skin damage score more than 1.5, while single dose irradiation resulted in skin damage scores up to 3. The three different strains, however, showed varying susceptibility to fractionated irradiation within the range under 1.5. C3H/HeMs did not display any skin reaction after irradiation with 40 Gy total dose, while C57BL/6J and A/J demonstrated various skin reactions. Different latent periods of damage were also observed among the strains after irradiation at each dose. Our data suggest that genetic factors cause obvious variations in severity of damage and latent period after fractionated irradiation.

Different radiation susceptibility among five strains of mice detected by a skin reaction.

Published reports about skin reactions to radiotherapy, especially among breast-cancer patients, suggest that there are interindividual differences in the normal tissue response, and genetic factors are thought to be involved in this variation. An analysis of murine strain differences may reveal the mechanism of genetic factors in the extent of normal tissue damage from irradiation for several endpoints. The variation in the radiation susceptibility was observed when the skin of mice from strains A/J, C3H/HeMs, C57BL/6J, C.B.17/Icr-scid and C3H-scid was irradiated with a single dose ranging from 10 to 60 Gy, using Cs-137 gamma rays. The active skin reaction of A/J mice lasted for months. C3H/HeMs mice showed dose-dependent skin damage, and consequently recovered to a state of mild damage within 40 days after local irradiation. The time course of the response in C57BL/6J mice was shorter than in A/J mice. The 2 strains of scid mice exhibited severe damage after irradiation at any dose from 20 to 50 Gy, and did not show any dose dependency. The variation between murine strains in macroscopic and histopathological changes in skin during the progression and resolution of damage caused by irradiation suggests an inter-strain variation in the expression of genes involved in injury, apoptosis, repair, and remodeling.

[Nursing care for the newborns with congenital Chagas' disease]. / ASSISTÊNCIA DE ENFERMAGEM AOS RECÉM-NASCIDOS COM DOENÇA DE CHAGAS CONGÊNITA.

In Brazil, due to the urbanization of the rural diseases, the health services must be prepared to detect precociously the infections, control the propagation and attend these sick people. The authors did a bibliographic surveying about congenital Chagas' disease, presented a study with a good evolution, tried to determine the nursing care to these newborns and the respectives objectives.

Strain-dependent differences in locomotor activity after local brain irradiation with 30 GyE of carbon ions.

This study investigated strain differences in brain damage among male A/J, C57BL/6JNrs and C3H/HeNrs mice after local brain irradiation. Whole brains were irradiated with a single dose of 30 GyE carbon ion beams and then locomotor activity was determined as body heat of each animal. The daily locomotor activities of untreated mice differed among strains. Non-irradiated C57BL/6JNrs mice were more active than A/J mice. This variance became more obvious immediately after irradiation, when the activity of A/J and C3H/HeNrs mice diminished, whereas that of C57BL/6JNrs mice increased at the beginning of the active phase and remained elevated for three days after irradiation. The altered activities of all three strains of irradiated mice gradually recovered to normal within three to four days.

Inter-strain variance in late phase of erythematous reaction or leg contracture after local irradiation among three strains of mice.

AIM: To gain insights into inter-strain differences in radiosensitivity. METHODS: Mice of inbred strains, A/J, C57BL/6J, and C3H/HeMs, were irradiated at graded doses ranging from 20 to 60 Gy. Skin reaction and leg contraction were observed for a period of 230 days and between 175 and 350 days, respectively. Gene expressions in leg skin tissue were quantified by quantitative RT-PCR assay at 1, 12 and 72 h after 30 Gy irradiation. Mice were locally irradiated by using a Cs-137 source. RESULTS: The three strains showed various degrees of susceptibility to irradiation has evaluated by skin scores. Large inter-strain differences were also detected in the lengths of contraction. Expressions of several genes such as Per3 and Rad51ap1 displayed inter-strain differences. CONCLUSIONS: The continuum model of tissue injury revealed that genetic factor, which varies among strains, is one of the causes of variances in severity of damage after irradiation.

Assistência de enfermagem aos recém-nascidos com doença de Chagas congênita / Nursing care for the newborns with congenital Chagas' diseases

No Brasil, devido à urbanizaçäo das enfermidades rurais tornou-se importante que os serviços de saúde estejam preparados para detectar precocemente essas infecçöes, controlar a propagaçäo e assistir esses doentes. As autoras fizeram um levantamento bibliográfico sobre a doença de Chagas congênita, apresentaram um caso com evoluçäo positiva e descreveram os cuidados de enfermagem e os respectivos objetivos