Search PubMed⌕ Search

Biomedical subjects

C J Gomer

Publications and source records attributed to C J Gomer.

At least 55 records · Page 3Linked to original sources
PubMed1986

Expression of potentially lethal damage in Chinese hamster cells exposed to hematoporphyrin derivative photodynamic therapy.

Experiments were performed to determine whether the expression and/or repair of potentially lethal damage could be observed in mammalian cells exposed to hemataporphyrin derivative (HPD) photodynamic therapy (PDT). Photodynamic therapy was combined with posttreatment protocols known to inhibit the repair of potentially lethal damage in cells treated with X-rays, ultraviolet radiation, or alkylating agents. Potentiation of lethal damage from photodynamic therapy was induced by hypothermia (4 degrees C) following short (1 h) or extended (16 h) HPD incubation conditions. Caffeine potentiated the lethal effects of PDT only when cells were incubated with HPD for extended time periods. However, 3-aminobenzamide had no effect on the cytotoxic actions of PDT following either short or extended HPD incubations. Recovery from potentially lethal damage expressed by posttreatment hypothermia was complete within 1 h, while recovery from potentially lethal damage expressed by posttreatment caffeine required time periods of up to 24 h. The lack of effect of 3-aminobenzamide on expression of potentially lethal damage following photodynamic therapy may be related to direct inhibition of adenosine diphosphoribose transferase by photodynamic therapy. These results indicate that the expression and repair of potentially lethal damage can be observed in cells treated with PDT and will vary as a function of porphyrin incubation conditions.

Animals↗
PubMed1985

In vitro and in vivo light dose rate effects related to hematoporphyrin derivative photodynamic therapy.

In vitro and in vivo experiments were performed to evaluate the parameter of light dose rate as it relates to the efficiency of hematoporphyrin derivative (HPD)-induced photosensitization. Exponentially growing Chinese hamster ovary cells were incubated with HPD (25 micrograms/ml) and were then exposed to red light (630 nm) delivered at different dose rates. A total of five dose rates (0.5, 5.0, 15, 23, and 60 milliwatts/sq cm) were examined following a 1-hr HPD incubation, two dose rates (1 and 20 milliwatts/sq cm) were examined after a 12-hr HPD incubation, and three dose rates (0.4, 4, and 40 milliwatts/sq cm) were examined following a 16-hr incubation and a 30-min serum wash protocol. The effect of light dose rate was determined from cell survival curves obtained by standard clonogenic colony formation assays. Similar levels of cellular toxicity were obtained when cells from each HPD incubation group were treated with equal doses of red light delivered at different dose rates. For in vivo experiments, albino mice were given injections of HPD (7.5 mg/kg) and 24 h later the right hind leg of each mouse was treated with localized red light (630 nm). A total dose of 270 J/sq cm was delivered to the right hind leg at dose rates of 5, 25, or 125 milliwatts/sq cm. The resulting acute skin damage induced by HPD photosensitization was scored over a 30-day period, and skin response curves for the three dose rates were obtained. Comparable levels of damage were induced in each of the three experimental groups. The results obtained from both in vitro and in vivo studies indicate that the photosensitizing efficiency of HPD photodynamic therapy is not affected by nonthermal variations in clinically relevant dose rates of delivered light.

Animals↗
PubMed1985

Photodynamic therapy of intraocular tumors: examination of hematoporphyrin derivative distribution and long-term damage in rabbit ocular tissue.

Studies were performed to determine the distribution of hematoporphyrin derivative (HPD) in ocular structures and to characterize long-term damage associated with ocular HPD photodynamic therapy. Pigmented rabbits with an amelanotic melanoma heterotransplanted to the iris were used to obtain quantitative tissue levels of HPD as well as to document HPD localization by fluorescence microscopy. HPD was administered i.v., and tissue concentrations of HPD were determined by spectrofluorometry following porphyrin extraction. Vascular structures such as the tumor, iris, and choroid-retina as well as the aqueous fluid from eyes containing tumors demonstrated rapid HPD localization. The sclera had minimal HPD uptake, and the drug was not detected in avascular structures such as the lens or cornea. HPD was cleared from all ocular structures except the tumor and choroid-retina by 24 h following injection. Fluorescence microscopy data indicate that HPD remained in the avascular photoreceptor cell outer segments of the retina. Long-term damage was documented in rabbits which received HPD photodynamic therapy to a 1-sq cm area of retina via transpupillary light delivery. Acute damage to the exposed area of retina (in the form of a chorioretinal scar) could be induced. This damage was permanent but not progressive. Lens opacities were not observed, and the cornea, aqueous, and vitreous remained clear on all test eyes. The results from these studies suggest that HPD photodynamic therapy may provide a selective and safe approach to the treatment of ocular tumors.

Animals↗
PubMed1984

Observations in studies of quantitative kinetics of tritium labelled hematoporphyrin derivatives (HpDI and HpDII) in the normal and neoplastic rat brain model.

Increasing interest has developed in the use of the photodynamic agent, Hematoporphyrin derivative (HpD) for photoradiation therapy (PRT) as adjunctive therapy of malignant glial tumors of the brain. HpD, injected systemically, is preferentially taken up and retained by neoplastic tissue. Early studies of such uptake have largely relied on gross fluorescence as evidence of tissue uptake. In this study HpD was labelled with a tritiated radioisotope (3H) in order to quantify tissue uptake in visceral and in normal and neoplastic brain tissues in a rat brain model. 3H-HpD was injected intravenously at a 10 mg/kg dose into 30 Sprague-Dawley rats (Group A) without tumors in order to clarify method. Separately, 3H-HpD of like dosage was injected into 20 Fischer-344 rats (Group B), 5 control and 15 with a 9L gliosarcoma implanted in the left anterior cerebral cortex. Post injection sacrifice occurred at 6, 24 and 48 hours. From the Sprague-Dawley group multiple somatic and cerebral specimens were assayed. Differential areas within the brain showed no significant difference in uptake. The tumor area, peritumoral margin, and distant uninvolved areas of the Fischer-344 9L rats were likewise assayed. Definite uptake of normal visceral and cerebral tissue occurred with a markedly higher uptake differential in tumor areas. Such differential was relatively consistent from trial to trial, but multiple separate values obtained in the respective study groups were often unreliabe in their reproducibility and at variance with previously reported tissue level studies. These findings implied an instability of 3H-HpD, subsequently confirmed chromatographically as contamination probably due to time related degradation and exchange. Therefore, 3H-HpD appears to inherently carry such a risk for contamination. The compound Photofrin II (HpDII) represents a chromatographic fraction of HpD (HpDI), currently considered its most photodynamically active and purest component. Tritiated Photofrin II was used for quantification. An assay was performed with 5 Fischer-344 9L brain tumor rats (Group C), sacrificed at 24 hours. Photofrin II provided results more reliably reproducible. Contamination, degradation, and exchange of 3H-Photofrin II did not appear to occur. Neoplastic brain levels of the Photofrin II isotope were higher than in the HpD studies, and highly fluorescent. Normal brain values were consistently minimal and without fluorescence. The differential tumor/brain ratio in Photofrin II was consequently much higher. The isolated active substrate of HpDI and HpDII (Photofrin II) appears to be the compound DiHematoporphyrin Ether (DHE).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Hematoporphyrin derivative photoradiation induced damage to normal and tumor tissue of the pigmented rabbit eye.

Cytotoxicity induced by hematoporphyrin derivative (HpD) photoradiation in both normal and experimental tumor tissue of pigmented rabbit eyes has been examined. In addition, documentation of HpD induced fluorescence in ocular structures has also been obtained. Acute normal ocular tissue toxicity studies demonstrated that HpD (1-10 mg HpD/kg) followed 48 hours later by a transpupil irradiation of red light (635 nm, 36-90 J/cm2) resulted in demarcated areas of retinal damage. Long term (chronic) toxicity studies have shown that the initial damage to the retina was permanent but that no damage to the cornea, lens or vitreous could be observed during a 16 month follow-up. Visual and histological documentation have been obtained, following HpD photoradiation therapy (PRT), in rabbit eyes having heterotransplanted single nodule amelanotic melanomas. A toxic effect characterized by tumor blanching, edema and hemorrhage was observed within 24 hours of treatment. Histological examination obtained 24 hours following HpD PRT illustrated massive tumor tissue necrosis and vascular disruption. HpD PRT at clinically relevant doses was also shown to be effective in selectively curing the highly malignant amelanotic iris melanoma. It is concluded that HpD PRT may prove to be an effective modality for treating certain ocular tumors.

Animals↗
PubMed1983

Hematoporphyrin derivative photoradiation therapy for the treatment of intraocular tumors: examination of acute normal ocular tissue toxicity.

Preclinical studies designed to define potential side effects resulting from the use of hematoporphyrin derivative (HPD) photoradiation therapy (PRT) as a modality for treating intraocular tumors have been performed. Pigmented rabbits were used to evaluate acute normal ocular tissue toxicity following single HPD PRT treatments in which the light was directed through the pupil and onto a 1-sq cm area of the retina. The treatment procedure consisted of the i.v. administration of HPD (1 to 10 mg/kg) followed 48 hr later by a 15-min exposure of localized red light [635 +/- 5 nm; 40 to 400 milliwatts/sq cm] generated by a free running rhodamine B dye laser pumped by a 5-watt argon laser. Toxicity to normal retinal tissue was documented using fundus photography, fluorescein angiography, and histological examination. The results of this study demonstrated that ocular damage in the form of retinal edema, detachment, and necrosis could be induced by clinically relevant doses of HPD PRT. The area of retinal damage was limited to the treatment field in all but the highest doses of HPD PRT. The histological results were in agreement with the visual observations in that abrupt and demarcated transition areas between injured and normal-appearing retina were observed. Care will have to be used in the delivery of light to the treatment field if HPD PRT is to be utilized for treatment of intraocular tumors.

Animals↗
PubMed1983

Comparison of mutagenicity and induction of sister chromatid exchange in Chinese hamster cells exposed to hematoporphyrin derivative photoradiation, ionizing radiation, or ultraviolet radiation.

Cell culture studies have been performed to compare the mutagenic potential and the induction of sister chromatid exchanges for hematoporphyrin derivative photoradiation, ionizing radiation, and UV radiation. The mutation frequency in Chinese hamster ovary cells at the hypoxanthine-guanine phosphoribosyltransferase locus was measured using resistance to 6-thioguanine. Phenotypic expression time prior to mutation selection was also examined. Treatment with either X-rays or UV was effective in producing mutants resistant to 6-thioguanine, but treatment with hematoporphyrin derivative photoradiation (at comparable toxicity levels) did not induce any mutagenic activity above background levels. The hematoporphyrin derivative incubation and photosensitization conditions used in this study did induce sister chromatid exchanges at frequencies comparable to those induced by X-rays but at lower frequencies than for UV treatments.

Animals↗
PubMed1982

Tissue distribution of 3H-hematoporphyrin derivative in athymic "nude" mice heterotransplanted with human retinoblastoma.

Quantitative uptake levels of tritium-labeled hematoporphyrin derivative (3H-HpD) have been obtained for normal and malignant tissue of athymic "nude" mice heterotransplanted intraocularly with human retinoblastoma. It was determined that eyes with tumor accumulated higher levels of 3H-HpD than those in control eyes. In addition, an improved therapeutic retention ratio of the drug (eyes with tumor compared with control eyes) was obtained at extended time intervals after administration.

Animals↗
PubMed1980

Acute skin phototoxicity in hairless mice following exposure to crude shale oil or natural petroleum oil.

The acute skin phototoxicity in hairless mice resulting from applications of crude shale oil or natural petroleum oil and exposure to near ultraviolet light has been investigated. In addition, the absorption and excitation-emission spectra of these oils have been described. While the application of crude shale oil alone was shown to elicit acute skin damage, the combination of the crude shale oil and near ultraviolet light induced skin damage much more severe than that produced by either agent alone. In contrast, the application of the natural petroleum oil and near ultraviolet light was less toxic than that of the crude shale oil in the absence of light. These results suggest that a potential health hazard exists from contact with shale oil compounds and exposure to near ultraviolet light from either the sun or artificial sources.

Animals↗
PubMed1980

DNA damage and repair in CHO cells following hematoporphyrin photoradiation.

The induction and repair of alkali labile lesions and single strand breaks in DNA of CHO cells following HpD photoradiation of X-irradiation has been examined. For treatments producing equal survival levels, the amount of DNA damage was less for HpD-photoradiated cells compared to X-irradiated cells. Both the time scale and the magnitude of repair of the DNA damage were the same for the 2 modalities, with the majority of repair occurring during the first 15 min of incubation and repair being essentially complete by 30 min.

Animals↗