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Biomedical subjects

R J Fry

Publications and source records attributed to R J Fry.

At least 19 recordsLinked to original sources

Photoreactivation of ultraviolet radiation-induced skin and eye tumors of Monodelphis domestica.

Chronic exposure of the opossum Monodelphis domestica to UV radiation (UVR) leads to the formation of cutaneous and corneal tumors. Groups of shaved opossums were exposed 3 times/week to: (a) UVR alone; (b) UVR followed immediately by 1 h of photoreactivating light (PRL) (320-700 nm); (c) 1 h of PRL followed by UVR; and (d) 1 h of PRL alone. Exposures were terminated after 70 weeks of treatment. Analysis of data plotted as probability of tumor formation versus weeks from first exposure shows that post-UVR exposure to PRL significantly (P less than 0.005) delayed the time to appearance of cutaneous tumors from a 50% probability of tumor formation at 73 weeks for those animals exposed to UVR alone to 128 weeks for those animals exposed to PRL after UVR. Pre-UVR exposure to PRL delayed the appearance of tumors by 6 weeks when compared to the UVR alone group, but the difference between the two groups was not statistically significant. The yield (number of tumors/surviving animal) of cutaneous tumors at 70 and 110 weeks following initiation of treatments also was significantly less in those animals exposed to PRL after, but not before, UVR. Based on the specificity of the PR repair pathway to act only on pyrimidine dimers, these results suggest that dimers are involved in the induction of cutaneous tumors. The results obtained with the induction of corneal tumors are more difficult to interpret. While exposure to PRL significantly delayed the appearance of corneal tumors, the magnitude of the effect was the same regardless of whether the PRL was given before or after each UVR exposure.

Animals

Detection of Chlamydia trachomatis endocervical infection in asymptomatic and symptomatic women: comparison of deoxyribonucleic acid probe test with tissue culture.

A deoxyribonucleic acid probe assay (PACE 2, Gen-Probe, San Diego) was compared with a standard tissue culture method for detection of Chlamydia trachomatis endocervical infection in both asymptomatic and symptomatic women. The results of the probe test were expressed as a ratio of relative light units of the specimen per relative light units of the cutoff recommended by the manufacturer. Samples with sample/cutoff ratios near 1.0 were repeated until two or more consistent ratios were obtained. A total of 426 specimens were obtained, with an overall disease prevalence of 10.1%. Of the 426 specimens examined, seven (1.6%) were near the cutoff and were retested. The results of 426 samples with matching cultures indicated that the manufacturer's discrete cutoff was adequate for results determination. The deoxyribonucleic acid probe test was essentially equivalent to standard tissue culture in terms of sensitivity, specificity, and positive and negative predictive values in a low-prevalence patient population.

Binding, Competitive

Comparison of Gen-Probe DNA probe test and culture for the detection of Neisseria gonorrhoeae in endocervical specimens.

A 2-h nonisotopic DNA probe assay for the direct detection of Neisseria gonorrhoeae in urogenital specimens has recently been modified (PACE 2; Gen-Probe, San Diego, Calif.). The new assay format was developed to increase the sensitivity of the assay and simplify procedural steps. In this study, the new DNA probe test was compared with a culture reference method for the detection of N. gonorrhoeae in endocervical specimens. The results of the DNA probe test were expressed as a ratio of relative light units (RLU) of the specimen/RLU of the cutoff recommended by the manufacturer. All patient samples with sample RLU/cutoff RLU ratios less than 0.7 were interpreted as negative, and ratios greater than 2.0 were interpreted as positive for gonorrhea. Samples with sample RLU/cutoff RLU ratios between 0.7 and 2.0 were repeated until two or more consistent negative or positive ratios were obtained. A total of 469 specimens were tested with an overall disease prevalence of 6.1%. Of the 469 patients tested, 5 specimens (1.0%) fell in this borderline region and were retested. If the manufacturer's recommended cutoff value had been used, the original DNA probe results would have resulted in two false-positives. Our data were analyzed for both symptomatic (prevalence, 11.7%) and asymptomatic (prevalence, 2%) women. The study indicated that with our modification of the manufacturer's endpoint interpretation, the DNA probe test was essentially equivalent to the culture method in terms of sensitivity, specificity, and positive and negative predictive values in both symptomatic and asymptomatic patient populations. The new DNA probe test can serve as a suitable screening and diagnostic test for the diagnosis of gonorrheal genital infections in women. Additionally, it offers the advantages of rapid turnaround time and ease of use and allows simultaneous testing for Chlamydia trachomatis on the same specimen.

Bacteriological Techniques

Health effects of ionizing radiation.

Although humans have evolved in an environment of ionizing radiation, it was not until man-made sources were developed that the effects of ionizing radiation started to become known. Detection and measurement of radiation is not only sophisticated but widely applied. This article deals with exposure to this kind of radiation and the risk it may cause.

Accidents

Radiation protection guidelines for the skin.

The past recommendations of the ICRP about dose limits to the skin are reviewed. Recently, an ICRP Task Group has been revisiting the old arguments and setting them against new data. With the exception of the function of cells in the skin associated with immunocompetence, non-stochastic effects have been well characterized and threshold doses are known with a precision appropriate for setting radiation protection standards. The current dose limitations of 0.5 Sv per year and a working lifetime dose limit of 20 Sv should protect the worker population against deterministic effects. When the ICRP made its recommendations in 1977 for dose limits there was no appreciation of the importance of the interaction of ultraviolet radiation (UVR) and X-rays. Both clinical and experimental data show that the risk of ionizing-radiation-induced cancer is significantly increased by subsequent exposures to UVR. Therefore, risks for sun-exposed areas of skin differ from those that are shielded. The risk estimate for skin cancer is very dependent on the selection of the projection model and on the mortality rate assumed. Based on the relative risk model a mortality rate of 0.2 per cent and summing risks for both UVR exposed and shielded skin the risk is about twice (1.94 x 10(-4) Sv-1) that which ICRP derived in 1977. With the absolute model the risk is considerably less, about 0.5 x 10(-4) Sv-1. There is still insufficient understanding of the effects of multiple or protracted exposures on the risk of skin cancer induction. Experimental results suggest that exposures, at least to relatively high total doses, that are protracted over a long period are more carcinogenic than a small number of exposures over a short period.

Animals

Cytotoxic effects of colcemid or high specific activity tritiated thymidine on clonogenic cell survival in B6CF1 mice.

High specific activity tritiated thymidine (HSA-[3H]TdR) and colcemid were given in cytotoxic doses and regimens to B6CF1/Anl mice. The number of cells per intestinal crypt was reduced by the S-phase-specific (HSA-[3H]TdR and the metaphase blocking and cytotoxic effect of multiple injections of colcemid. In 50-day-old mice, the cytotoxic effect of multiple injections of colcemid reduced both the number of cells per crypt and the clonogenic cell survival. However, the number of surviving intestinal clonogenic or stem cells, assayed by the microcolony technique, did not change in 110--130-day old mice. These data suggest that most of the cells at risk from these cytotoxic agents are not clonogenic in adult 110--130-day old mice but are the cells in amplification division. However, since the stem cells of young mice are more susceptible to colcemid, they are apparently in a more rapid cell cycle than those of older mice. The clonogenic cell survival measured in 110--130-day old mice after a single radiation dose of 14 Gy (1400 rad) responded in a non-linear way to increasing time of continuous colcemid cytotoxicity. These data suggest that the intestinal stem cells can respond to amplification compartment cell death by a shortening of their cell cycle and thus, over time, the number of stem cells at risk to colcemid cytotoxicity increases.

Animals

Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice.

Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carconogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in gamma-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H2O2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H2O2.

Amitrole

Photosensitized reactions and carcinogenesis.

We present data from experiments designed to investigate the role of DNA interstrand cross-links induced by exposure to 8-MOP plus UVR and skin carcinogenesis. 8-MOP was administered topically to two strains of hairless mice, SKH:hairless-1 and HRS/J/An1, which were then exposed to UV light sources with emission in the range of 1) 300-400, 2) 320-400, and 3) predominantly 365 nm. We found no strain dependency for DNA cross-link production, but a marked strain-dependent difference in tumor susceptibility was noted. Only a small strain-dependent difference occurred in tumor incidence when TPA was administered after exposure to 8-MOP and 320-400 nm. These results suggest that the events concerned with tumor promotion are dependent on strain. Because the most effective tumorigenic wavelength spectrum was 300-400 nm, we investigated the possibility of interaction between lesions induced by the 300- to 320-nm wavelengths and the psoralen photoadducts. In the course of this experiment, we found that the tumorigenic effect was also dependent on the time interval between exposures to 8-MOP plus 365-nm light.

Animals

Radiation injury: some aspects of the oncogenic effects.

The late effects or irradiation stem from cell killing, mutation, and malignant transformation. Cancer is the major somatic late effect of exposure to low dose levels of radiation, and estimates of risk of cancer in man after irradiation are based entirely on human experience. The data for dose-response relationships for the induction of tumors by external irradiation in man have been obtained from a single exposure or a small number of exposures delivered at high dose rates. In contrast, exposure to environmental irradiation is mainly protracted over a long period of time and is delivered at a low dose rate. As yet no allowance has been made for the effect of protraction of the exposure time in estimating the risk of cancer, although an adjustment has been made in the case of estimates of genetic risk. Incidence of tumors has been the only parameter used for risk estimates, but latent period and degree of malignancy, which are probably both dose and dose-rate dependent, influence the nature of the risk from radiation. As the knowledge about the effects of low-level radiation has been accumulated and assimilated over the last 70 years, so has the concern for reasonable standards of safety. There are still problems in the estimation of radiation risks, but at least many of the relevant questions can now be framed. The problems of estimating risks for chemical carcinogens are clearly greater, but the experience gained from radiation studies should help in the design of the necessary experiments.

Age Factors

Induction and persistence of pyrimidine dimers in the epidermal DNA of two strains of hairless mice.

The ultraviolet-light induction of DNA damage has been measured in the epidermis of hairless mice with the use of damage-specific endonucleases from Micrococcus luteus. The rates of induction of endonuclease-sensitive sites in HRS/J/Anl and Skh:hairless-1 mice were 6.1 +/- 0.5 X 10(-11) and 6.5 +/- 0.8 X 10(-11)/dalton/J/sq m from a FS40 fluorescent sun lamp (280 to 400 nm), respectively. Enzymatic photoreactivation with yeast photoreactivating enzyme showed that approximately 80% of the endonuclease-sensitive sites were cycloburyl pyrimidine dimers. In both strains of mice the pyrimidine dimers remained in high-molecular-weight DNA for 24 hr after irradiation. These data show that mouse epithelial cells in vivo have little or no capacity for the excision repair of pyrimidine dimers.

Animals