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D W Whillans

Publications and source records attributed to D W Whillans.

At least 19 recordsLinked to original sources
PubMed2003

Structure of a physiologically based biokinetic model for use in 14C and organically bound tritium dosimetry.

Physiologically based biokinetic (PBBK) dosimetry models for beta emitters such as 3H and 14C must include rapid turnover compartments which, while they may be minor in terms of dose commitment, can dominate bioassay measurements at early times after intake. In this paper, a consistent PBBK model structure will be described for use in dose assessments for organic 14C and organically bound tritium (OBT), and also for 14CO2, based on the literature of human carbon metabolism, and on direct measurements of human excretion. CO3/HCO3- is a central compartment in carbon metabolism. The 14CO2 biokinetic model described in ICRP Publication 80 for the calculation of dose coefficients was found to omit early components of excretion necessary for the accurate interpretation of bioassay results. Recommendations on the requirements on dosimetry models for intakes of 14C and OBT are made.

Air Pollutants, Radioactive↗
PubMed1980

An analysis of changes in oxygen tension in stirred cellular suspensions under conditions of radiolytic and cellular consumption.

The determination and maintenance of constant known low levels of oxygen is critical in the study of chemical radiosensitization of mammalian cells in vitro. Both radiosensitization and toxicity effects must be observed, however, in systems were significant consumption of oxygen both by radiation and by cellular metabolism takes place during the experiment. We have analyzed the form of these changes in oxygen tension in stirred cellular suspensions with overlying gas phase under conditions of consumption and found it to conform to the relationship (C[t] - C infinity) = (C[o] - C infinity)e-k1t with C infinity = Cg - R/k1. Here C[t] is the oxygen tension throughout the solution, Cg is the equivalent level in the overlying gas phase, R (concentration units per second) is the depletion rate, and k1 (second-1) is a physical constant independent of oxygen concentration and depletion rate. This relationship has been confirmed in detail using a Clark-type oxygen sensor and a high-stability amplifier design due to Koch with which oxygen levels down to a few hundred parts per million can be determined with accuracy. From these data consumption rates of 4.3 +/- 0.5 ppm O2/rad by radiation in alpha-medium at 27 degrees C, and of (2.9 +/- 1.3) x 10(-17) moles O2/cell/second by metabolizing CHO cells at 37 degrees C have been determined, in agreement with literature values.

Animals↗
PubMed1978

Rapid-mixing studies of the mechanisms of chemical radiosensitization and protection in mammalial cells.

A continuous flow, rapid-mixing system has been constructed to measure the degree of radiosensitization or protection observable after incubation of Chinese hamster ovary cells at room temperature for periods from about 5 to 1000 ms with a number of radiation modifiers. In agreement with Adams et al. (1975) full sensitization by oxygen is obtained in only a few tens of milliseconds. Misonidazole (10 mM) sensitizes at very nearly the steady-state level (E.R. approximately 2.3) in about 300 ms. Similarly near maximum sensitization by 10 mM metronidazole is seen within the same period. For large effects to be observed in such short times makes unlikely the involvement of any biochemical modification of either the drug or cells. Radioprotection by 1 M dimethyl suplhoxide reaches about 80% of the equilibrium control value within 850 ms. However, if its mode of action involves scavenging of hydroxyl radicals in competition with cellular components, the necessity for very high concentrations in the immediate region of the cellular target would be expected to require longer diffusion times. Cysteamine (10 mM) shows no evidence of its substantial protective ability even after 850 ms incubation. This molecule, which alone in this group exists as an ion in neutral solution, may encounter considerable difficulty in entering the cells.

Cell Survival↗
PubMed1975

Studies of electron migration in DNA in aqueous solution using intercalating dyes.

The reactions of the hydrated electron (e-aq) and of the hydroxyl radical (OH) with double-stranded DNA in aqueous solution at room temperature have been studied through the use of the intercalating dyes, proflavine and ethidium. These dyes react with e-aq with rate constants of (2.5 +/- 0.2) - 10(10) M-1 - s-1 and (3.0 +/- 0.3) - 10(10) M-1 - s-1, respectively; the rate constant for the reaction of OH with proflavine is (1.0 +/- 0.2) - 10(10) M-1 - s-1. When these molecules are bound within the DNA structure both the yields and the rate constants of reaction with e-aq are reduced in a manner entirely consistent with a simple competition between the DNA bases and restricted dye molecules reacting with a bimolecular rate constant of about 2 - 10(9) M-1 - s-1. No evidence of free electron migration in the DNA was obtained, and an upper limit of five base pairs for the range of such migration was derived. Reactions of the hydroxyl radical with DNA-bound proflavine also lead to a rate constant of about 2 - 10(9) M-1 - s-1. These rate constants are in good agreement with rate predictions (per base unit) for a diffusion-controlled reaction with the DNA structure.

Acridines↗
PubMed1975

Electron transfer oxidation of DNA radicals by paranitroacetophenone.

The reaction of a typical electron-affinic sensitizer, paranitroacetophenone (PNAP) with the model compounds thymine, thymidine, thymidylic acid, deoxyribose and single and double-stranded DNA has been investigated by pulse radiolysis. Radicals formed by one-electron reduction of the bases and of DNA react rapidly and efficiently with PNAP by electron transfer. A small yield of transfer (less than 10 per cent) is also observed arising from oxidation of the radicals formed by the small proportion of OH which react at the sugar moieties in DNA. In contrast, electron transfer oxidation by PNAP of radicals formed by the addition of OH to the base moieties, e.g. thymine, is not an efficient process. Further, addition of the sensitizer to the thymine OH-adduct proceeds at a rate that is too low to measure by pulse radiolysis. We conclude that, since the major sites of OH reaction with DNA are the heterocyclic bases (greater than 80 per cent), oxidation of the resultant radicals is unlikely to be a major step in the mechanism of sensitization by this typical hypoxic-cell sensitizer.

Acetophenones↗
PubMed1975

Studies of the mechanisms of radiosensitization of bacterial and mammalian cells by Diamide.

Diamide sensitizes bacterial and mammalian cells to radiation by at least two mechanisms. Sensitization of V79-GL1 Chinese Hamster cells is due mainly to a reduction of a reduction of the survival-curve shoulder, is observed both in oxygen and in hypoxia,and is additive to the sensitization of hypoxic cells by some nitroimidazoles. In contrast, sensitization of the radioresistant organism, Micrococcus sodonensis, which has apronounced shoulder, is entirely dose-modifying. In a rapid-mix study using Serratia marcescens, two mechanisms of sensitization have been identified. After 4 to 40 msec preirradiation contact with Daimide, the enhancement ratio is constant at 1.6; after 10min contact, it is 2.5. With V79-GL1 cells, no sensitization occurs in the short-time-range; likewise non is seen when Diamide is added to bacteria or mammalian cells 4 msec after irradiation. It is concluded that Diamide sensitizes by at least two mechanisms, one of which resembles that of the electron-affinic type.

Animals↗