The modulation of radiation-induced damage to pig skin by essential fatty acids

Hopewell, J. W.; Robbins, Michael E.; Aardweg, G.J.M.J. van den; Morris, G. M.; Ross, Graham; Whitehouse, Elizabeth; Horrobin, David F.; Scott, Catherine

doi:10.1038/bjc.1993.276

Cited by 43 publications

(14 citation statements)

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“…In the Dutch Large White pig irradiated with HDR 192 Ir, moderate/severe erythema occurred after 39¡9 days, while moist desquamation was seen after 35¡9 days, dusky mauve erythema after 56¡9 days and dermal necrosis after 82¡8 days. These data were not signi®cantly different from those obtained for the English Large White pig [39,41] with a latent period of 36¡3 days for moist desquamation and of 76¡3 days for dermal necrosis. The dose±effect relationships of the late skin reactions are presented in Figure 4.…”

Section: Resultscontrasting

confidence: 50%

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

Hamm¹,

Bakker²,

Berg³

et al. 2000

The British Journal of Radiology

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Abstract. An experimental brachytherapy model has been developed to study acute and late normal tissue reactions as a tool to examine the effects of clinically relevant multifractionation schedules. Pig skin was used as a model since its morphology, structure, cell kinetics and radiation-induced responses are similar to human skin. Brachytherapy was performed using a microSelectron high dose rate (HDR) afterloading machine with a single stepping source and a custom-made template. In this study the acute epidermal reactions of erythema and moist desquamation and the late dermal reactions of dusky mauve erythema and necrosis were evaluated after single doses of irradiation over a follow-up period of 16 weeks. The major aims of this work were: (a) to compare the effects of iridium-192 ( 192 Ir) irradiation with effects after Xirradiation; (b) to compare the skin reactions in Yorkshire and Large White pigs; and (c) to standardize the methodology. For 192 Ir irradiation with 100% isodose at the skin surface, the 95% isodose was estimated at the basal membrane, while the 80% isodose covered the dermal fat layers. After HDR 192 Ir irradiation of Yorkshire pig skin the ED 50 values (95% isodose) for moderate/severe erythema and moist desquamation were 24.8 Gy and 31.9 Gy, respectively. The associated mean latent period (¡SD) was 39¡7 days for both skin reactions. Late skin responses of dusky mauve erythema and dermal necrosis were characterized by ED 50 values (80% isodose) of 16.3 Gy and 19.5 Gy, with latent periods of 58¡7 days and 76¡12 days, respectively. After Xirradiation, the incidence of the various skin reactions and their latent periods were similar. Acute and late reactions were well separated in time. The occurrence of skin reactions and the incidence of effects were comparable in Yorkshire and Large White pigs for both X-irradiation and HDR 192 Ir brachytherapy. This pig skin model is feasible for future studies on clinically relevant multifractionation schedules in a brachytherapy setting.

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Section: Resultscontrasting

confidence: 50%

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

Hamm¹,

Bakker²,

Berg³

et al. 2000

The British Journal of Radiology

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“…Interestingly, in separate studies conducted on normal tissues in vivo, it has been reported that dietary GLA decreases the severity of radiation damage to the skin (Hopewell et al, 1993) and CNS (Hopewell et al, 1994). We have previously shown that GLA supplementation can decrease clonogenic cell survival of malignant rat astrocytoma cells and increase their radiosensitivity (Vartak et al, 1997).…”

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confidence: 99%

γ-Linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes

Vartak

McCaw²,

Davis³

et al. 1998

Br J Cancer

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Summary This study compares the effect of y-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B1 0 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.Keywords: polyunsaturated fatty acids; y-linolenic acid; linoleic acid; astrocytoma; astrocyte; radiation Gamma linolenic acid (GLA, 18:3n6) supplementation has been reported to suppress the growth of tumour cells in vitro (Fujiwara et al, 1986;Sangeetha and Das, 1992;Falconer et al, 1994) and in vivo (Karmali et al, 1985;Abou et al, 1987). Interestingly, in separate studies conducted on normal tissues in vivo, it has been reported that dietary GLA decreases the severity of radiation damage to the skin (Hopewell et al, 1993) and CNS (Hopewell et al, 1994). We have previously shown that GLA supplementation can decrease clonogenic cell survival of malignant rat astrocytoma cells and increase their radiosensitivity (Vartak et al, 1997). To determine the therapeutic potential of this observation, it is important to investigate the effect of GLA on 'normal' rat astrocytes. The purpose of this work was to compare the effects of GLA on the survival of 36B10 astrocytoma cells and astrocytes and their response to radiation. The uptake and use of GLA by astrocytoma cells has also been compared with that by astrocytes.The cytotoxic action of polyunsaturated fatty acids (PUFAs) is thought to be mediated predominantly via lipid peroxidation and free radical generation (Begin et al, 1988;Ells et al, 1996). Several studies also indicate that eicosanoid and leukotriene synthesis play an important role in tumour cell proliferation and metastasis (Earashi et al, 1995; Damtew and Spagnuolo, 1997). Arachidonic acid (AA, 20:4n6) and dihomo-y-linolenic acid (DGLA, 20:3n6) are the substrate for the biosynthesis of prostaglandins of the 2-and 1-series respectively (Crawford, 1983 Bell JG et ...

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“…6,8,9,15 In addition, anti-inflammatory effects are being investigated for benefit in ameliorating adverse effects of radiation therapy. 7,41,42 Potential benefits of dietary n-3 fatty acid therapy must be weighed against the possibility of untoward effects. In this study, we evaluated the effects of dietary supplementation on select aspects of hemostasis.…”

Section: Discussionmentioning

confidence: 99%

Platelet Function in Dogs Treated for Lymphoma and Hemangiosarcoma and Supplemented with Dietaryn‐3 Fatty Acids

McNiel

Ogilvie

Mallinckrodt

et al. 1999

Veterinary Internal Medicne

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A prospective randomized, double-blind clinical trial was performed to test the hypothesis that dogs with malignancies that are supplemented with n-3 fatty acids do not have clinical or laboratory evidence of coagulation disorders or altered platelet function when compared with unsupplemented dogs with similar malignancies. Thirteen dogs with hemangiosarcoma and 66 dogs with lymphoma were evaluated. Coagulation status of the dogs with lymphoma and hemangiosarcoma was evaluated with prothombin time, partial thromboplastin time, platelet count, and in vitro platelet aggregometry using the whole-blood method. These tests were performed at 5 time points: before beginning the diet (week 0), at weeks 3, 15, and 21, and at 1 year or when progressive disease was evident. Alterations in platelet function in dogs receiving a diet supplemented with dietary n-3 fatty acids were not identified when compared to dogs fed a control diet. Dietary n-3 fatty acid supplementation using this dosage and ratio in dogs with lymphoma or hemangiosarcoma did not induce clinically significant hemorrhage in these animals. Therefore, supplementation with n-3 fatty acids did not result in clinical or laboratory evidence relating to uncontrolled hemorrhage in these dogs.Key words: Cancer; Docosahexaenoic acid; Eicosanoids; Eicosapentaenoic acid; Fish oil.T he therapeutic value of dietary n-3 fatty acid supplementation is currently being investigated in the management of diseases, including cancer.1-14 The mechanism for antitumor effects of n-3 fatty acids is poorly understood but may involve the preferential incorporation of the n-3 series fatty acids over fatty acids of the n-6 series into the cell membrane. The altered fatty acid composition may result in altered cell membrane function including cell interaction with extracellular matrix, cellular signaling pathways, receptor function, and the arachidonic acid cascade. 1,2,8,15,16 All cells are subject to these effects, including platelets. Dietary n-3 fatty acid supplementation and metabolism have been shown to result in antithrombotic effects.1-3 Antithrombotic effects are largely attributable to decreases in platelet function with increases in bleeding time and decreases in the magnitude of in vitro platelet aggregation responses. These effects on platelet function have been explored in humans, laboratory rodents, cats, and in normal dogs. [17][18][19][20][21][22][23][24][25] Clinically relevant bleeding has not been demonstrated. However, concern exists about the potential adverse effects in patients that have uncertain coagulation status.17 Conversely, the potential for decreasing platelet function may also be of considerable benefit in patients with hypercoagulability.Human cancer patients are subject to a variety of hemostatic defects, which are also frequently identified in dogs with cancer. [26][27][28][29][30][31][32][33][34][35] Platelet function in dogs with malignancies may be enhanced compared to that in normal dogs. 35 Because the hemostatic system is altered in cancer patient...

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The modulation of radiation-induced damage to pig skin by essential fatty acids

Cited by 43 publications

References 31 publications

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

γ-Linolenic acid (GLA) is cytotoxic to 36B10 malignant rat astrocytoma cells but not to 'normal' rat astrocytes

Platelet Function in Dogs Treated for Lymphoma and Hemangiosarcoma and Supplemented with Dietaryn‐3 Fatty Acids

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