Mahendra K. Logani

Lipid oxidation: Biologic effects and antioxidants—A review

The detection and measurement of lipid oxidation in biological systems and some biologic effects of this oxidation are reviewed. The role of lipid oxidation in the process of photocarcinogenesis and the protective effect of antioxidants against this process also are discussed. The mechanism of such protection is unknown and studies directed at elucidating the mechanism of antioxidant effect in photocarcinogenesis and in some other pathological conditions believed to involve, lipid oxidation are needed. In addition to this, epoxidation of lipids observed in monolayer studies requires further investigation, particularly in the presence of some other unsaturated molecules. The possible significance of such a study—particularly in the presence of polycyclic aromatic hydrocarbon carcinogens, where formation of epoxides is generally accepted as active intermediates-is also discussed. In addition, present knowledge on the role of lipid peroxides in the destruction of proteins and biomembranes, in chemically induced toxicity and in generation of singlet oxygen is presented.

PHOTOOXIDATION OF 8‐METHOXYPSORALEN WITH SINGLET OXYGEN

Abstract— The in vitro photooxidation of 8‐methoxypsoralen (8‐MOP) with singlet oxygen is studied. Irradiation of 8‐MOP(295–400 or320–400 nm) in the presence of oxygen for 72 h results in the formation of a product (1.4%) which is identified as 6‐formyl‐7‐hydroxy‐8‐methoxycoumarin by aid of IR, NMR, MS and co‐chromatography with an authentic sample. A study of this reaction in the presence of l,4‐diazobicyclo(2,2,2)octane, a singlet oxygen scavenger, indicates the involvement of 1O2 in the formation of this compound. In addition to this, formation of a novel dimer of 8‐MOP is reported.

Micronuclei in peripheral blood and bone marrow cells of mice exposed to 42 GHz electromagnetic millimeter waves

Abstract Vijayalaxmi, Logani, M. K., Bhanushali, A., Ziskin, M. C. and Prihoda, T. J. Micronuclei in Peripheral Blood and Bone Marrow Cells of Mice Exposed to 42 GHz Electromagnetic Millimeter Waves. Radiat. Res. 161, 341–345 (2004). The genotoxic potential of 42.2 ± 0.2 GHz electromagnetic millimeter-wave radiation was investigated in adult male BALB/c mice. The radiation was applied to the nasal region of the mice for 30 min/day for 3 consecutive days. The incident power density used was 31.5 ± 5.0 mW/cm2. The peak specific absorption rate was calculated as 622 ± 100 W/kg. Groups of mice that were injected with cyclophosphamide (15 mg/kg body weight), a drug used in the treatment of human malignancies, were also included to determine if millimeter-wave radiation exposure had any influence on drug-induced genotoxicity. Concurrent sham-exposed and untreated mice were used as controls. The extent of genotoxicity was assessed from the incidence of micronuclei in polychromatic erythrocytes of peripheral blood and bone marrow cells collected 24 h after treatment. The results indicated that the incidence of micronuclei in 2000 polychromatic erythrocytes was not significantly different among untreated, millimeter wave-exposed, and sham-exposed mice. The group mean incidences were 6.0 ± 1.6, 5.1 ± 1.5 and 5.1 ± 1.3 in peripheral blood and 9.1 ± 1.1, 9.3 ± 1.6 and 9.1 ± 1.6 in bone marrow cells, respectively. Mice that were injected with cyclophosphamide exhibited significantly increased numbers of micronuclei, 14.6 ± 2.7 in peripheral blood and 21.3 ± 3.9 in bone marrow cells (P< 0.0001). The drug-induced micronuclei were not significantly different in millimeter wave-exposed and sham-exposed mice; the mean incidences were 14.3 ± 2.8 and 15.4 ± 3.0 in peripheral blood and 23.5 ± 2.3 and 22.1 ± 2.5 in bone marrow cells, respectively. Thus there was no evidence for the induction of genotoxicity in the peripheral blood and bone marrow cells of mice exposed to electromagnetic millimeter-wave radiation. Also, millimeter-wave radiation exposure did not influence cyclophosphamide-induced micronuclei in either type of cells.

Destruction of cutaneous melanoma with millimeter wave hyperthermia in mice

Millimeter wave irradiation has been found to generate a dose-dependent heating of skin, providing an opportunity for destruction of heat-sensitive cutaneous tumors including melanomas. In vitro irradiation of epidermal keratinocytes and melanoma cells revealed distinct susceptibility of melanoma cells to MMW hyperthermia with higher thermotolerance of keratinocytes. No significant species differences were found when human and murine keratinocytes and melanoma cells were compared. In vivo irradiation of cutaneous melanoma in mice with MMW at the incident power density of 1.25 W/cm/sup 2/ for 30 min resulted in a selective melanoma destruction. Histological analysis showed no tissue damage of normal skin cells (necrosis or apoptosis) within the exposed skin areas. We hypothesize that MMW irradiation would be a useful treatment modality for cutaneous melanoma in humans.

A novel photorearrangement of 7,12-dimethylbenz(a)anthracene-7,12-epidioxide into 6b,11b-dihydro-6b,11b-dimethyl-benzofuro[3,2-b]naphtho[1,2-d]furan

Bei der Photolyse des 7,12-Dimethylbenz(a)anthracens (II) erhalt man neben dem fruher beschriebenen Endoperoxid (I) ein weiteres Reaktionsprodukt der Struktur (III).

Millimeter Wave and Drug Induced Modulation of the Immune System -Application in Cancer Immunotherapy

In recent years several approaches have been used for the treatment of cancer. These include surgery, chemotherapy, radiotherapy, and immunotherapy. Immunotherapy includes systemic administration of cytokines, adaptive transfer of activated T cells, NK cells, dendritic cells and macrophages. Immunotherapy is used to stimulate and train the patient’s immune system to fight against cancer. However, this approach alone is not sufficient. Therefore, a combination of immunotherapy with conventional chemo- and radiation therapy is commonly used for the treatment of cancer. But systemic administration of cytokines, such as interferons and interleukins, commonly used for immunotherapy, have their own toxic side effects that can be life threatening to many patients. In this article, we have reviewed the current knowledge of the effects of millimeter wave therapy (MMWT) on the immune system. MMWT, an alternative and complementary modality of treatment, is widely used for the treatment of cancer and many other diseases in Russia and several East European countries. However, it is virtually unknown to Western physicians. Our experimental studies have shown that MMWT when used in combination with chemotherapy protects the immune system from the toxicity of chemotherapy without introducing any additional toxicity of its own. Furthermore, our studies have shown that the combined millimeter wave- and chemotherapy can reduce the tumor metastasis, and tumor resistance to chemotherapeutic drugs. Thus combined therapy using MMWT provides a promising new strategy for the treatment of cancer.

Neutral lipids from the skin of the Rhino mutant mouse

The neutral lipids of the skin of the Rhino mutant mouse consist mainly of fatty acid esters of sterols, fatty alcohols and 1,2-alkane diols, with strikingly low amounts of triacylglycerols. Fatty acids of wax and sterol esters were predominantly even chain monounsaturates (63 per cent) between C16 and C36 with a surprisingly high proportion of long chain lengths: the principal peaks corresponded to C32, C34, C18, C30, and C22 monoenes. The fatty alcohols showed a somewhat similar pattern, but with an even greater preponderance of long chain lengths and only small proportions shorter than C24. sterols included cholesterol, as expected, but only to the extent of about 28 per cent; the larger fraction was shown to be lathosterol (5alpha-cholest-7-en-3beta-ol). The largest single fraction (35.6 per cent) of cutaneous lipids consisted of fatty acid esters of 1.2-alkane diols. The 1,2-alkane diols were completely saturated and included odd and even chain lengths, both straight and branched, in the C16-C24 range: predominant peaks were C20, C22(iso), C16, and C22. Fatty acids of diol esters ranged between C14-C36 with major concentrations of C18, C22, C32, and C34 monounsaturates and C20 and C16 saturates.

Composition of novel triesters from the skin of the rhino mutant mouse

Composition of two novel triesters, derived from the skin of the rhino mutant mouse, is described. Chemical and spectroscopic analysis of the products of pancreatic hydrolysis of the triesters showed that these are comprised predominantly of isomer I (92.7 mole %). The syntheses of two reference compounds, 1-O-hexadecanoyl-2-[(14-hexadecanoyloxy)O-tetradecanoyl] 1,2-hexadecanediol (Ia) and 2-O-hexadecanoyl-1-[(14-hexadecanoyloxy)O-tetradecanoyl]-1,2-hexadecanediol (IIa), corresponding in their structures to isomers I and II of the triester, wax have also been described.

Effect of millimeter waves and cyclophosphamide on cytokine regulation.

We have reported previously that millimeter waves (MMWs) protect T-cell functions from the toxic side effects of cyclophosphamide (CPA), an anticancer drug. Since the effect of MMWs has been reported to be mediated by endogenous opioids, the present study was undertaken to investigate the role of endogenous opioids in protection of T-cell functions by MMWs. The effect of MMWs (42.2 GHz, incident power density = 38 mW/cm2) was studied on CPA-induced suppression of cytokine release by T cells in the presence of selective opioid receptor antagonists (ORA). Production of cytokines was measured in CD4 T cells isolated from splenocytes. Treatment of mice with CPA suppressed the formation of Th1 cytokines (TNF-α, IFN-γ, and IL-2), shifting the overall balance toward Th2 (IL-4 and IL-5). MMW irradiation of CPA-treated groups up-regulated the production of Th1 cytokines suppressed by CPA. Treatment of the CPA+MMW group with selective kappa (κ) ORA further potentiated this effect of MMWs on Th1 cytokine production, whereas treatment with μ or δ ORA increased the imbalance of cytokine production in the Th2 direction. These results provide further evidence that endogenous opioids are involved in immunomodulation by MMWs.

Continuous millimeter-wave radiation has no effect on lipid peroxidation in liposomes.

The effect of millimeter waves on lipid peroxidation was studied in the presence and absence of melanin. Irradiation of liposomes with continuous millimeter electromagnetic waves at frequencies of 53.6, 61.2 and 78.2 GHz and incident power densities of 10, 1 and 500 mW/cm2, respectively, did not show an enhancement in the formation of lipid peroxides compared to unirradiated samples. Liposomes exposed to 254 nm UVC radiation at 0.32 mW/cm2 and 302 nm UVB radiation at 1.12 mW/cm2 served as positive controls. No increment in the formation of lipid peroxides was observed when irradiation of liposomes was carried out in the presence of ADP-Fe+3 and EDTA-Fe+3. Direct irradiation of melanin with millimeter waves did not exhibit an increased formation of superoxide or hydrogen peroxide. The present results indicate that millimeter waves of the above frequencies and intensities do not cause lipid peroxidation in liposomal membranes.