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Biomedical subjects

D B Leeper

Publications and source records attributed to D B Leeper.

At least 73 records · Page 4Linked to original sources
PubMed1976

The effect of adriamycin and radiation on G2 progression.

The effect of the DNA-intercalating antibiotic adriamycin on the progression of Chinese hamster ovary cells into mitosis, and on the delay induced by ionizing radiation, was studied using the mitotic cell selection procedure to monitor the rate of cell division. Following the addition of adriamycin, the mitotic rate remained unaltered for a refractory period and then decreased to zero. This effect was concentration dependent with transition points between the S-G2 boundary for 0.1 mug/ml and late G2 for 250 mug/ml. Cells treated with either a 10- or 30-min pulse of 1.0 mug adriamycin per ml exhibited a refractory period identical to that observed for continuous treatment. However, after a delay of congruent to 3.5 or congruent to 5 hr, respectively, cell division resumed. The mitotic rate of cells that received 150 rads of X-ray at the oneset of an adriamycin pulse declined coincident with that of radiation only, but resumed coincident with those receiving adriamycin only. This implies that radiation-induced division delay (congruent to 3 hr) was repaired before cells recovered from adriamycin-induced division delay and that the two agents were not additive. This lack of synergism is in contrast to that observed for cell lethality.

Cell Division↗
PubMed1975

The effect of age on the long-term response of bone marrow to local fractionated irradiation.

The in-field long-term progressive response of bone marrow to localized fractionatedradiation to the thoracic spine was observed in weanling and adult rats. Total dose levels were 1800,3600 and 5400 rads given in daily fractions of 180 rads for 900 rads perweek, to simulate the clinical setting. Animals were sacrificed at 4 1/2, 6, 8, and 10months after irradiation, and bone marrow from within the treated area was ezamined. The juvenile marrow repopulated to higher levels of cellularity and after higher doses of radiation than the adult. The degree of marrow depletion, time of repopulation, and ultimate level of repopulation after cessation of irradiation were all dependent on the total dose. Some of the suggested clinical implications include re-evaluation of the lower doses given to children.

Age Factors↗
PubMed1975

Blood pressure changes in mice after lethal staphylococcal infection and endotoxin challenge.

A radioisotope technique has been used to determine blood pressure changes in mice after lethal staphylococcal infection and after lethal endotoxin challenge. The method was verified by making simultaneous direct measurements in rats. Mice in both groups became hypotensive to a similar level (a fall 20-30 mm Hg). This tailcuff technique is simple and reliable but is dependent upon normal tail blood flow. Spurious low pressure readings are obtained in hypothermic or chilled mice because the tail is a major thermoregulator organ. These difficulties can be overcome by warming chilled or hypothermic mice.

Animals↗
PubMed1973

Repair kinetics of radiation-induced mitotic delay.

The recovery from radiation-induced mitotic delay in asynchronous sarcoma-180 (S-180) ascites tumor cells has been analyzed in a manner analogous to the repair of sublethal damage. 200-R increments were separated by various fraction intervals (not exceeding the time necessary for mitosis to return to control levels) for total exposures up to 1600 R. The accumulated mitotic delay after the last exposure increment, in percent of an equivalent single exposure, decreased exponentially with overall treatment time in a bimodal fashion. An initial repair process displayed a half time of 2.3 h of overall elapsed time and was followed by a slower process with a half time of 15.1 h. Such a bimodal recovery provides an explanation of why fractionation intervals long with respect to the amitotic period resulting from a single 200 R exposure enhance mitotic delay over that of equivalent single exposures, while shorter fractionation intervals diminish it. It also predicts that mitotic delay vs. dose curves should bend toward the abscissa as the exposure time is increased with large single exposures and large fractionated exposures given over short fraction intervals.

Animals↗
PubMed1971

Chromosomal aberrations and mortality of x-irradiated mammalian cells: emphasis on repair.

Chromosomal aberrations induced by x-rays in synchronized Chinese hamster cells correlated well with mortality as the radiosensitivity was made to vary by a factor of 4 by treating the cells with colcemid or 5-bromodeoxyuridine and by irradiating the cells in different parts of the cell cycle. 37% survival was observed when the cells sustained about one aberration per cell. Furthermore, the positive correlation was observed during repair of damage. Repair was measured by the reduction in damage observed either as the incubation period between two doses was increased (repair of sublethal lesions), or as the cells were held at 20 degrees C after a single dose of radiation (repair of potentially lethal lesions). Repair of both sublethal and potentially lethal lesions occurred with a half-time of about 12 min and was inhibited at 0 degrees C. These correlations strongly support the hypothesis that x-ray-induced cell death results from damage in chromatin structures.

Animals↗
PubMedDate not supplied

Lucanthone modification of cyclophosphamide toxicity in the Chinese hamster.

The interaction of lucanthone and cyclophosphamide (CYC) was investigated in the Chinese hamster in terms of the LD50/7 and LD50/30. These values may be indicative of gastrointestinal stem cell depletion and bone marrow stem cell depletion, respectively. When a nonlethal dose of 100 mg/kg lucanthone preceded CYC injection, the LD50/7 for CYC reached its minimum value of 470 mg/kg at a treatment interval of 10 hours. Lucanthone administered simultaneously with CYC had no effect on the control LD50/7 of 750 mg/kg, and by 48 hours after lucanthone administration the LD50/7 had returned to the control value. When CYC administration preceded that of lucanthone, the LD50/7 reached a minimum of value of 610 mg/kg at an interval of 5 hours; however, for the entire sequence it was approximately 640 mg/kg over all intervals up to 48 hours. The LD50/30 for CYC was only slightly reduced by the presence of lucanthone, indicating that bone marrow sensitivity to CYC was only marginally affected by lucanthone. These data indicate that lucanthone may interact with CYC damage in much the same way as it interacts with radiation damage, viz, by reducing cellular capacity to accumulate and repair sublethal damage.

Animals↗
PubMedDate not supplied

Betulinic acid sensitization of low pH adapted human melanoma cells to hyperthermia.

Betulinic acid is a known inducer of apoptosis in human melanoma that is most effective under conditions of low pH. It was hypothesized that betulinic acid, in combination with acute acidification and/or hyperthermia, would induce higher levels of apoptosis and cytotoxicity in low pH-adapted human melanoma cells than in cells grown at pH 7.3. DB-1 human melanoma cells, adapted to a tumour-like growth pH of 6.7, were exposed to hyperthermia (2h at 42 degrees C) and/or betulinic acid (4-10 microg/ml) and compared with cells grown at a physiological pH of 7.3 or after acute acidification from pH 7.3-6.3 or pH 6.7-6.3. Betulinic acid induced higher levels of apoptosis and cytotoxicity in low pH-adapted cells than in cells grown at pH 7.3, as measured by the terminal deoxynucleotidyl transferase (TdT) DNA fragmentation assay (TUNEL), the MTS cell viability assay, and single cell survival. Acute acidification of low pH adapted cells rendered them more susceptible to betulinic acid-induced apoptosis and cytotoxicity. In the presence of hyperthermia at 42 degrees C for 2 h, cells grown at pH 7.3 were not sensitized to heat killing by betulinic acid, whereas cells grown at pH 7.3 and acutely acidified to pH 6.3, cells adapted to growth at pH 6.7 and cells adapted to growth at pH 6.7 and acutely acidified to pH 6.3 were all similarly sensitized to heat killing by betulinic acid, with survival values of 5, 9 and 2%, respectively. It is concluded that betulinic acid may be useful in potentiating the therapeutic efficacy of hyperthermia as a cytotoxic agent in acidotic areas of tumours with minimal effect in normal tissues growing at pH 7.3.

Apoptosis↗