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Biomedical subjects

D B Leeper

Publications and source records attributed to D B Leeper.

At least 55 records · Page 3Linked to original sources
PubMed1982

Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP.

The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 micrograms/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 micrograms/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 micrograms/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 micrograms/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered.

Animals↗
PubMed1981

The effect of reduced pH on the induction of thermotolerance.

The effect of low pH on thermotolerance induction was studied in Chinese hamster ovary cells. The thermotolerance ratio (TTR), defined as the ratio of the Do of a subsequent heat survival curve following heat challenge to the Do of the single-dose heat survival curve, was found at pH 7.2 to be maximal at 3.6 seven hours following a 10-min 45 degrees initial heat dose. When heating and induction times were at pH 6.6, the TTR ws reduced to 3.1. When the pH was reduced to 6.6 only during the induction period, the TTR was even lower at 2.5. Heat sensitization at low pH was distinguishable from inhibition of thermotolerance induction. Both the heat sensitization and reduced thermotolerance induction at low pH may enhance the thermal response of tumors relative to normal tissues.

Animals↗
PubMed1979

The effect of lucanthone on the radiation response of intestinal stem cells in Chinese hamsters.

Crypt microcolony assay was used to determine the effect of lucanthone on the radiation response of intestinal stem cells in Chinese hamsters . The Dq of the crypt microcolony radiation--survival curve was maximally reduced by 205 rads when lucanthone injection preceded irradiation by 10 hours and was reduced by 140 rads when injection followed irradiation by 5 hours. On simultaneous injection and irradiation, Dq was reduced by only 20 rads; when injection and irradiation were separated by approximately 30 hours, Dq returned to the control value. Lucanthone never affected Do. Thus at non-toxic concentrations, lucanthone reversibly modifies cellular ability to accumulate and repair sublethal radiation damage without affecting radiation sensitivity.

Animals↗
PubMed1978

Effect of lucanthone hydrochloride on the radiation response of intestine and bone marrow of the Chinese hamster.

A sublethal dose of 100 mg lucanthone hydrochioride/kg (Miracil D, Nilodin; NSC-14574) administered ip into Chinese hamsters [median lethal dose for 30-day survival (LD50/30) of 315 mg/kg] reduced the radiation tolerance of the small intestine and had little or no effect on the radiation tolerance of the bone marrow. Lucanthone hydrochloride was administered at various times before and after whole-body 60Co gamma-irradiation. The median lethal dose for 7-day survival (LD50/7), indicative of death from gastrointestinal epithelial denudation, was reduced from 1,235 rads to minimum values of 995 rads or 985 rads by lucanthone hydrochloride inoculation 10 hours before irradiation or 7.5 hours post irradiation, respectively. The LD50/30, indicative of death from bone marrow stem cell depletion, remained unaltered at approximately 990 rads over the entire treatment scheme, which indicated that the radioresponsiveness of bone marrow stem cells was unaffected by lucanthone hydrochloride. The lucanthone hydrochloride effect was reversible in that control values of LD50/7 were attained by 40 hours post inoculation. Serum concentration of lucanthone hydrochloride in the Chinese hamster, determined spectrophotometrically, reached a peak of 8 microgram/ml by 1.5 hours post inoculation and then decreased exponentially with a half-life of approximately 6 hours, so that by 30 hours post inoculation it was unmeasurable.

Animals↗
PubMed1977

125I-UDR induced division delay.

Mitotic selection for cell cycle analysis was used to investigate the effects of (3)H and (125)I, incorporated into DNA, on the cell cycle progression of Chinese hamster ovary (CHO) cells. The results indicate that S-phase cells were delayed and G(2) cells were not.

Cell Line↗
PubMed1976

Combinations of hyperthermia (40 degrees, 45 degrees C) with radiation.

Incubation of Chinese hamster cells at an elevated but sublethal temperature between fractions of radiation and/or pulses of hyperthermia at 45 degrees C strongly modified the effectiveness of cell killing. Increasing the incubation temperature from 37 to 40 degrees C between fractions of hyperthermia at 45 degrees C followed by radiation substantially enhanced cell killing; while the opposite sequence (radiation leads to incubation at 40 degrees C leads to hyperthermia at 45 degrees C) resulted in less effective cell killing than would have been expected from the independent interaction of hyperthermia and radiation alone. This suggests the use of short pulses of localized hyperthermia in the presence of physiologically tolerable fever followed by irradiation as one approach to the utilization of hyperthermia in cancer therapy.

Animals↗