Begell House Inc.
Journal of Environmental Pathology, Toxicology and Oncology
JEP(T)
0731-8898
26
3
2007
A New Method for Photodynamic Therapy of Melanotic Melanoma—Effects of Depigmentation with Violet Light Photodynamic Therapy
165-172
10.1615/JEnvironPatholToxicolOncol.v26.i3.10
Li-Wei
Ma
Department of Radiation Biophysics, Institute for Cancer Research, Rikshospital-Radiumhospital HF and Plasma/Room Physics, University of Oslo, Oslo, Norway
Kristian Pagh
Nielsen
Department of Physics and Technology, University of Bergen, Bergen, Norway
Vladimir
Iani
Department of Radiation Biophysics, Institute for Cancer Research, Rikshospital-Radiumhospital HF and Plasma/Room Physics, University of Oslo, Oslo, Norway
Johan
Moan
Department of Radiation Biophysics, Institute for Cancer Research, Rikshospital-Radiumhospital HF and Plasma/Room Physics, University of Oslo; lnstitute of Physics, University of Oslo, Blindern, Oslo, Norway
Melanotic melanomas have a poor response to photodynamic therapy (PDT). The reason for this is that melanin absorbs light over the entire wavelength region used for PDT (400−750 nm). Photobleaching of melanin is an approach to overcome this obstacle. In the present work, reflectance spectroscopy was applied to study depigmentation of human and murine skin with different melanin contents, and effects induced by PDT with topical application of methyl 5-aminolevulinate (MAL) on B16F10 melanotic melanomas transplanted to nude mice. Depigmentation and inhibition of tumor growth after violet light (420 nm) exposure, red light (634 nm) exposure, and combinations of both were studied. Reflectance spectroscopy was suitable for evaluation of the pigmentation of both human and murine skin. Skin depigmentation leads to increase in reflectance. PDT with violet light bleached some of the melanin in the skin above the B16F10 melanomas, and possibly also in the upper part of the melanomas. This resulted in a larger growth inhibition of tumors first given PDT with violet light and then with red light compared to treatments using the reverse order of illumination, namely, red light before violet light. It is concluded that violet light PDT can bleach melanin in melanotic tumors and therefore increase their sensitivity to red light PDT. This finding indicates a new PDT modality that can be further developed for treatment of superficial melanotic melanomas and possibly other diseases where pigmentation is a problem.
Heat Shock Protein 27 Protects against Aminolevulinic Acid-Mediated Photodynamic Therapy-Induced Apoptosis and Necrosis in Human Breast Cancer Cells
173-183
10.1615/JEnvironPatholToxicolOncol.v26.i3.20
Sarah A.
Ziegler
Department. of Chemistry, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4003, USA
Cherisse
Loucks
Department. of Chemistry, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4003, USA
Steen J.
Madsen
Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, 4505 S. Maryland Pkwy., Box 453037,
Las Vegas, NV 89154, USA
Stephen W.
Carper
Department. of Chemistry, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-4003; and Department of Health Physics, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV 89154-3037, USA
This study utilized two breast cancer cell lines differing only in their expression of heat shock protein 27 (hsp27). The DB46 cell line was engineered to express high constitutive levels of hsp27, while the DC4 cell line expresses normal low levels of hsp27. The cells were incubated in 1 mM aminolevlinic acid (ALA) 4 hr prior to light exposures (635 nm) ranging from 1 to 20 J/cm2. Both cell lines displayed a dose response to photodynamic therapy (PDT) as assayed by clonogenic survival. LD50s of 2.68 and 1.27 J/cm2 were observed for DB46 and DC4 cells respectively. ALA-PDT-induced resistance to both apoptosis and necrosis in the DB46 cell line was found from TUNEL assays and fluorescence microscopy studies using propidium iodide and Hoechst staining.
Protective Effect of Diltiazem (a Calcium Channel Blocker) against Cadmium-Induced Toxicity in Mice
185-193
10.1615/JEnvironPatholToxicolOncol.v26.i3.30
Vandana
Nunia
Radiation & Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur—302 004, India
Pradeep Kumar
Goyal
Radiation and Cancer Biology Laboratory, Department of Zoology, University of Rajasthan, Jaipur - 302 004, India
Protective efficacy of diltiazem (a calcium channel blocker) has been studied against cadmium chloride (CdCl2) induced hematological and biochemical alterations in Swiss albino mice. CdCl2 (5 mg/kg b.wt.; i.p.) with or without prior treatment of diltiazem (100 mg/kg b. wt.; i.p.) was given to six-week old mice. Significant increase in the number of bone marrow cells as well as hematological parameters was observed in diltiazem pretreated CdCl2 intoxicated animals. A significant increase in lipid peroxidation (LPO) and acid phosphatase (ACP) level, and decrease in glutathione (GSH) and alkaline phosphatase (ALP) level in blood as well as liver were measured in CdCl2 intoxicated mice, while such values were near normal in DTZ pretreated animals. Furthermore, a significant increase in erythropoeitin (EPO) level was observed in diltiazem (DTZ) pretreated CdCl2 intoxicated animals as compared to CdCl2 alone treated animals. Thus, Diltiazem administration before cadmium intoxication protects bone marrow and hematological constituents in mice.
Protective Effects of Picorrhiza Kurroa Extract against 2-Acetylaminofluorene-Induced Hepatotoxicity in Wistar Rats
195-205
10.1615/JEnvironPatholToxicolOncol.v26.i3.40
Sarwat
Sultana
Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences amia Hamdard, New Delhi, India
Sahar
Rahman
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India
Picrorrhiza kurroa has been shown to impart significant hepatoprotective activities, partly by modulation of free radical—induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with hepatic injury. The effect of P. kurroa treatment on the antiproliferative response and, hepatic antioxidant enzymes of rats administered with 2-acetylaminofluorene (2-AAF) was studied in Wistar rats. 2-AAF (50 mg/kg body weight, i.p.) enhances hepatic lipid peroxidation, with reduction in hepatic glutathione content, glutathione peroxidase, glutathione reductase, catalase, and glutathione-s-transferase. There was an increase in the levels of transa-minase enzymes and LDH. 2-AAF treatment also enhanced ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with P. kurroa extract (250 and 500 mg/kg body weight) resulted in significant decrease in lipid peroxidation, transaminase enzymes, LDH, hepatic ODC activity, and DNA synthesis (p < 0.001). Hepatic glutathione content (p < 0.001), glutathione metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered to significant level (p < 0.001).
In Vitro Mitigation of Arsenic Toxicity by Tea Polyphenols in Human Lymphocytes
207-220
10.1615/JEnvironPatholToxicolOncol.v26.i3.50
Dona
Sinha
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, Kolkata, India
Subhabrata
Dey
Central Research Instrumentation Facility, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India
Rathindra Kumar
Bhattacharya
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026
Madhumita
Roy
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India
The groundwater arsenicals have brought dreadful misery for the people residing in the endemic regions of West Bengal, India. Arsenic-related anomalies include arsenicosis, hyperkera-tosis, gastric complications, liver fibrosis, peripheral neuropathy, and cancer. Some of these diseases have been frequently associated with overproduction of reactive oxygen species that cause DNA damage and improper functioning of body's antioxidant defense mechanism. Natural polyphenols present in tea serve as excellent antioxidants. In the present study, an attempt has been made to elucidate the role of representative polyphenols and extracts of green and black tea in modulating sodium arsenite (As III)−induced DNA damage in normal human lymphocytes. Comet assay was used to detect the DNA damage. Arsenic-induced oxidative stress was measured with generation of reactive oxygen species, lipid peroxidation, and activity of some antioxidant enzymes. Expression of some repair enzymes such as poly(ADP-ribose) polymerase and DNA polymerase β was measured to assess the effect of tea on DNA repair. Tea afforded efficient reduction of As III−induced DNA damage in human lymphocytes. Tea also quenched the excessive production of reactive oxygen species by arsenic, reduced the elevated levels of lipid peroxidation, and increased the activity of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase. Furthermore, tea enhanced recovery of DNA damage, which was indicative of repair as confirmed by unscheduled DNA synthesis and pronounced expression of DNA repair enzyme poly(ADP-ribose) polymerase. It is speculated that the antioxidant potential and repair-inducing capacity of tea might help in combating the severe genotoxic effects induced by arsenic in the human population.
Status of Selenium, Vitamin E, and Vitamin A among Saudi Adults: Potential Links with Common Endemic Diseases
221-243
10.1615/JEnvironPatholToxicolOncol.v26.i3.60
Iman
Al-Saleh
King Faisal Specialist Hospital & Research Centre
Inaam
El-Doush
Biological & Medical Research Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
Grisellhi
Billedo
Biological & Medical Research Department, King Faisal Specialist Hospital & Research Centre, P.O. Box: 3354, Riyadh, Saudi Arabia
Gamal El-Din
Mohamed
Biostatistics, Epidemiology & Scientific Computing Department, King Faisal Specialist Hospital & Research Centre, P.O. Box: 3354, Riyadh
Gamal
Yosef
Biological & Medical Research Department, King Faisal Specialist Hospital & Research Centre, P.O. Box: 3354, Riyadh, Saudi Arabia
This study was designed to determine the status of selenium, dl-α-tocopherol, and all-trans-retinol in adults living in Al-Kharj district using serum and toenail samples, and to look for possible association between these parameters and the etiology of endemic diseases in the same area. For this purpose, we examined a cross section of samples of 743 healthy Saudi adults on routine visits to the Primary Health Care Unites (PHCUs) for different common health problems. The arithmetic mean for selenium, dl-α-tocopherol, and all-trans-retinol in serum and toenail selenium levels were 107.045 ± 23.045 μ;g/l (n = 743, range 52.600−210.120 μ;g/l), 1.053 ± 0.324 mg/dl (n = 737, range 0.29−3.42 mg/dl), 52.561 ± 25.671 μ;g/dl (n = 743, range 11.20−400.85 μ;g/dl), and 0.634 ± 0.221 μ;g/g (n = 691, range < DL − 1.797 μ;g/g), respectively. The average serum selenium concentration seems to be satisfactory and compares favourably with high selenium intake countries. Although none of our participants exhibited serum selenium deficiency (< 45 μ;g/l), 41% of our participants had toenail selenium < 0.56 μ;g/g reported low levels in the previous study. The mean serum dl-α-tocopherol concentrations fall within the upper limit of the normal range of > 0.698−1.981 mg/dl for α-tocopherol as found in previous studies. On the other hand, the mean serum all-trans-retinol is higher than the normal range (20−30 μ;g/dl). None had exhausted retinol stores trans-retinol and MDA levels in the serum was found as a sign of peroxidative lipid damage, confirming the role of vitamin A in reducing oxidative stress. Our data also revealed a link between the status of selenium, dl-α-tocopherol and all-trans-retinol and a number of health problems. However, these observations need larger epidemiological studies for further confirmation.