Some public attitudes about health and the environment.

Public opinion is formed both by long-term developments and--at the other extreme--by single unanticipated events. This suggests that readers of opinion survey findings should note field interviewing dates and further determine what the news media have been reporting about relevant developments and events. Personal health and the cost of health care are high on the public's agenda; this is an important backdrop to a review of public attitudes and priorities related to health and the environment. What about the environment? Americans increasingly believe that we are not spending enough on environmental protection and improvement. The public thinks of environmentalists in a favorable light, and a very sizeable minority believe they have too little influence--the same number who feel it's "about right." Our surveys have shown that the more people perceive an environmental threat to their safety, well-being and health, the more they will want regulation or industry action to meet the threat. High on the public's anxiety list are hazardous wastes (especially their disposal) and the transport and use of toxic materials in manufacturing and processing, industrial accidents involving the release of pollutants, the leakage of chemical waste into the soil, and the pollution of water and air from industrial sources. Our data support the assumption that for the foreseeable future these and certain other ecological dangers will be seen as serious by large majorities of Americans. For example, even the safety of drinking water has slowly become more questionable in the public's mind.(ABSTRACT TRUNCATED AT 250 WORDS)

Many combinations of ring structures and sensitizing groups have been synthesized and tested for potential use as radiotherapy adjuvants to overcome the resistance of hypoxic tumour cells to ionizing radition. Among the drugs tested have been nitroxyl compounds Cooke et al. (1976), nitrofurans Chapman et al. (1973), nitropyrroles Raleigh et al. (1978), nitroimidazoles Asquith et al. (1974), non-nitro compounds Wardman et al. (1982), and indoles Infante et al. (1980). Of the compounds examined, misonidazole (MISO) and desmethylmisonidazole, have entered clinical trials, but optimal doses of drug with each radiation dose fraction are not possible due to a cumulative neurotoxicity.
MISO mimics oxygen and functions as a radiosensitizer because of its electron affinity; this is the so-called "rapid" component of biological sensitization Adams, (1982). A prolonged incubation of MISO under hypoxia leads to the depletion of cellular thiols and results in an additional component of radiosensitization (the biological "slow" component) as well as a sensitization to some chemotherapy agents Stratford et al. (1980). The extent to which MISO and other similar compounds produce the preincubation effects correlates well with the amount of cell killing produced, i.e. the chemosensitization from prolonged hypoxic incubation is linked inexorably with cytotoxicity.
In the search for compounds superior to MISO, it might prove fruitful to consider separately the requirements for radiosensitization and chemosensitization. In the case of chemosensitization a compound is needed that reacts rapidly to deplete cellular thiols. In this case hypoxic cell cytotoxicity is probably unavoidable, although we do not know whether there is either a direct link, or even a one-to-one correlation, between cytotoxicity in the petri dish and the troublesome dose-limiting neurotoxicity in the human. For radiosensitization alone, a compound showing minimal cytotoxicity may be advantageous which could then be used at much higher concentrations. This is the approach used in the development of the triazole (1-methyl-3-nitro-1,2,4 triazole 3-NTR), tested in this report.
Chinese hamster V79 cells grown in Ham's FIO supplemented with 10% foetal bovine serum, antibiotics and L-glutamine were used in this study. The procedure for the treatment of cells has been described previously. Briefly, log phase cells grown in Corning 150 cm2 tissue culture flasks were trypsinized and resuspended in complete growth medium. Aerated and hypoxic cells at a concentration of 2x 105 cellsml-l were treated in glass spinner vessels based on the design of Chapman et al., 1974. Hypoxia was induced by degassing with high purity N2 for a period of 1 h, followed by addition of degassed drug to obtain the desired final drug and cell concentration. The cells were then incubated at 37.5°C for 1 h with drug prior to irradiation or samples removed at desired intervals for cytotoxicity determinations. Aliquots were plated into flasks with fresh medium, incubated for 7 days and fixed and stained.
The X-ray source was a Sieman's Stabilipan; 300k Vp, 12 mA, 0.2mm Cu; based on measurement with a Victoreen ionization chamber, the dose-rate at the treatment distance of 25 cm was calculated to be 6.3 Gymin-1. Figure 1 bare from a representative experiment in which hypoxic or aerated V79 cells were treated with drug at 37.5°C for a period of 1 h and during the immediately following exposure to graded doses of X-rays. Figure 2 comprises pooled data from several experiments (including those in Figure 1) expressing the enhancement ratio (ER) as a function of drug concentration. ER is defined as the ratio of doses for cells treated under hypoxic conditions without drug to hypoxic cells treated with drug to obtain an equal biological effect. Survival data for hypoxic or aerated V79 cells treated at 37.5°C with 3-NTR are shown in Figure   3.

Data in
The data show that 3-NTR is a very efficient radiosensitizer, specific for hypoxic cells, needing approximately one-half the concentration of MISO to obtain an equal ER. Furthermore, 3-NTR at the ©) The Macmillan Press Ltd., 1983 Received 23 September 1982, accepted 7 October 1982.  adjuvant to radiotherapy. The sensitizing efficiency of aromatic nitro compounds is directly correlated with their electron affinity. These properties are commonly increased by introducing electron withdrawing substituents on the ring. A second method to decrease the It-density of a heterocyclic system is to incorporate into the ring system a pyridine type (X-deficient) nitrogen. This would exert approximately the same electron withdrawing effect as the introduction of an electron affinic substituent. Indeed, 3-NTR exhibits approximately a 100-fold increase in sensitizing efficiency over the corresponding 4-nitroimidazole, Adams et al. (1979). This compound and related analogues merit further testing using in vivo systems to ascertain whether these structures posses the requisite pharmacological stability for use in vivo.