Radiomimetic effect

Thacker, J. (1976) Radiomimetic effects of hydrogen peroxide in the inactivation and mutation of yeast. Radiat. Res., 68, 371-380... 

Mustard is an alkylating agent similar to drugs that have been used in cancer chemotherapy, such as nitrogen mustards, Cytoxan, and cis-platin. Since DNA is one of mustard s most sensitive targets, it is not surprising that carcinogenesis and radiomimetic effects are seen. ... 

Casualties who have liquid mustard burns over 50% or more of body surface area or burns of lesser extent but with more than minimal pulmonary involvement pose a problem for the triage officer. An estimated LD50 (ie, the dose that is lethal to 50% of the exposed population) of liquid mustard, 100 mg/ kg, will cover 20% to 25% of body surface area. It is unlikely that a casualty will survive 2 LD50 because of the tissue damage from the radiomimetic effects of mustard. Two LD50 of liquid will cover about 50% of body surface area, and casualties with a burn this size or greater from liquid mustard should be considered expectant. They will require intensive care (which may include care in an aseptic environment because of leukopenia) for weeks to months, which can be provided only at the far-rear echelons or in the continental United States. Chances of survival... 

Homolysis of carbon-halogen bonds occurs easily by sonication of alkyl halides, as liquids or in solution. The energy of an aliphatic C-Cl bond is ca. 325 kJ moLL A thermolytic mechanism in the bubble is generally invoked, but if a radiomimetic effect exists, ionization can occur in analogy with the radiolysis of chlorocarbons. 

On the other hand, the existence of a sonochemical effect, for most cases observed when quinones are used or an oxidizer is present, suggests the sonochemical formation of some oxidized intermediate from the diene. That it forms directly via a radiomimetic effect or with the participation of a species derived from the solvent is difficult to decide, but we mentioned several times in this discussion that the sonochemical effect is suppressed by some solvents, demonstrating that the medium should not act only as a physical energy carrier, but also probably plays a chemical role. The presence of radical cations derived from the diene is compatible with the positive results by Mason, Snyder, Villacampa, Fillion,4 52 ifiigY negative results found by Reisse can also be... 

It acts by cross-linking of DNA. It also has radiomimetic property. It is bound to plasma proteins and is excreted slowly unchanged in urine. It is effective in metastatic testicular and ovarian carcinoma, advanced bladder carcinoma and refractory squamous cell head and neck carcinoma. 

Hicks SP (1954) The effects of ionizing radiation, certain hormones, and radiomimetic drugs on the developing nervous system. J Cell Physiol, 43(Suppl 1) 151-178. 

International symposium, Genetic Effects of Radiation and Radiomimetic Chemicals ... 

Trichothecenes cause apoptosis and/or necrosis in the lymphoid, hematopoietic, and gastrointestinal systems resulting in leukopenia, vomiting, and diarrhea that can be lethal. In addition, trichothecenes are toxic to the skin and testes. Immune suppression and increased susceptibihty to infection may occur, especially in the late phase of the disease. The toxic effects from trichothecenes largely resemble those following radiation exposure (radiomimetic) due to effects on rapidly dividing cells in the intestine, bone marrow, and testis. 

Elson, L. A. Radiation and radiomimetic chemicals. Comparative physiological effects. London Butterworths 1963. 

The T-2 mycotoxins have a low molecular mass of 250-500 Da, are nonvolatile compounds produced by filamentous fiingi or molds of the genus Fusarium, and are extremely stable in the environment. Of the multiple mechanisms of actions, many are poorly understood. However, their most notable effect stems from their ability to rapidly inhibit protein and nucleic acid synthesis. Thus, they are markedly cytotoxic to rapidly dividing cells, such as in the bone marrow, G1 tract (mucosal epithelium), skin, and germ cells. This cytotoxic effect imitates the hematopoietic and lymphoid effect of radiation sickness, thus the mycotoxins are referred to as radiomimetic agents. The mycotoxins also alter ceU-membrane strucmre and function, inhibit mitochondrial respiration, and inactivate certain enzymes. Decontamination requires the use of hypochlorite solution under alkaline conditions, such as 1% sodium hypochlorite and 0.1 M NaOH with 1 h contact time (USAMRICD, 2005). 

Table 6. Effect of thiosulphate and cysteine on LD50 of nitrogen mustards. Reproduced from the paper by Connors, T.A., Jeny, A and Jones, M. (1964), Reduction of the toxicity of radiomimetic alkylating agents in rats by thiol pretreatment-III. The mechanism of the protective action of thiosulphate. Biochem. Pharmacol., 13, 1545-1550... 

Many chemical substances when administrated to the body show the same effects as irradiation. Because cancer caused by radiation has been investigated more than cancer induced by chemicals, such substances are called radiomimetic (mimetic -= imitative). In order to qualify as a radiomimetic agent, the substance must do the following stop cell division, stop tumor formation, produce chromosome aberrations, cause mutations, kill lymphocytes, and be carcinogenic. Chemical substances which meet a few, but not all of these requirements are not considered radiomimetic. The effects depend on the concentration of the substance e.g. cell division is interrupted by many radiomimetic substances at concentrations 10 mole 1 ... 

Typical radiomimetic substances are organic peroxides (e.g. ethylene oxide), ethylene di-imine, mustard gas and derivatives, aliphatic dichloro-amines, etc. These compounds or chemical groups occur in many familiar materials such as tobacco smoke. The effect of a certain amount of a radiomimetic substance can be calculated to correspond to a radiation dose. Thus, smoking a pipe of tobacco corresponds to an average radiation dose of about 0.04 mSv. 

Conklin JW, Upton AC, Christenberry KW (1965) Further observations on late somatic effects of radiomimetic chemicals and X-rays in mice. Cancer Res 25 20-28. 

Radiating (nuclear) weapons produce energy in the form of an explosive blast, in addition to gamma rays and neutrons that destroy unprotected tissue, particularly DNA. (Thus, mustard agents and T2 mycotoxin, because of their similar effects, are sometimes referred to as radiomimetic. ) Enhanced radiation warheads, or neutron bombs, minimize the destruction of materials while maximizing lethalities among enemy personnel. 

Radiomimetic Radioprotective Radioprotective effect Respiratory depressant Respiratory stimulant RNA synthesis inhibition... 

The answer b 4 [Chapter 101VB I b(2J/. Radiomimetic syndrome, which is a complex of effects that result from excessive radiation exposure, can also be caused by some cancer chemotherapeutic agents. These agents are powerful antimitotic chemicals that may also cause necrosis, especially of metabolically active and rapidly dividing cells. Intestinal crypt cells are in actively mitotic and serve as the source of mature cells that populate the villous Intestinal epithelium. Loss of crypt cells causes eventual loss of the epithelial lining of the intestines, with resultant diarrhea and intestinal hemorrhage. 

B. M. Cattanach, A genetical approach to the effects of radiomimetic chemicals on fertility in mice, in Effects of Ionizing Radiation on the Reproductive System (W. D. Carlson and F. X. Gassner, eds) pp. 415-426, Pergamon Press, Oxford, London, New York, Paris (1964). 

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