Radiation protection: Anti Radiation Vaccine Technology.

Radiation Protection. Anti-
Radiation Vaccine. Isolation of
Radiation Toxins from Irradiated
Plants .
Dmitri Popov MD (Russia), PhD (Russia-Canada)
Advanced Medical Technology and Systems Inc.
intervaccine@gmail.com
Prof. Jeffrey Jones, Baylor Medical School, USA.

Radiation Effects. Toxicity of Plants after
irradiation.
• Research Proposal: Radiation Protection. Anti-Radiation Vaccine.
Isolation of Radiation Toxins from Irradiated Plants .
• Dmitri Popov
• Full-text · Research Proposal · Jan 2016
• File name: RadiationProtectionAntiRadiationVaccine.pptx
DOI: 10.13140/RG.2.1.3094.4403

irradiation.
Keywords: Radiation; Apoptosis; Necrosis; programmed cell death;
intrinsic/extrinsic pathway; granzyme A/B; perforin.

Radiation Protection. Technology of Anti
Radiation vaccine.
• Programmed cell death (PCD) occurs in animals and plants under
various stresses include different types of radiation.
• The ability to modulate the life and prevent death of an irradiated
cells is recognized as a great therapeutic potential.
• Apoptosis also occurs as a defense mechanism such as in immune
reactions or when cells are damaged by disease or physical or
chemical agents.

Radiation vaccine.
• Irradiation with any type of radiation or viruses, group of drugs used
for cancer chemotherapy results in DNA damage in some cells, which
can lead to apoptotic death through a p53-dependent pathway.

Radiation vaccine.
After irradiation is also the issue of distinguishing apoptosis from necrosis,
two processes that can occur independently, sequentially, as well as
simultaneously (Hirsch, 1997; Zeiss, 2003).
Can immunological mechanisms induce apoptosis or necrosis?
Yes.
Can inhibition of pathological, immunological mechanisms prevent apoptosis
or even necrosis?
Inhibition of pathological, immunological could prevent massive apoptosis.
Inhibition of pathological, immunological could prevent massive necrosis.
Possible yes.

Radiation vaccine.
• At low doses, a variety of injurious stimuli such as heat, radiation,
hypoxia and cytotoxic anticancer drugs can induce apoptosis but
these same stimuli can result in necrosis at higher doses.
• Toxicologic Pathology, 35:495–516, 2007 Copyright C by the Society of Toxicologic
Pathology ISSN: 0192-6233 print / 1533-1601 online DOI:
10.1080/01926230701320337
• Apoptosis: A Review of Programmed Cell Death SUSAN ELMORE NIEHS,
Laboratory of Experimental Pathology, Research Triangle Park, North Carolina
27709, USA

Radiation vaccine.
• Although the mechanisms and morphologies of apoptosis and
necrosis differ, there is overlap between these two processes.
Evidence indicates that necrosis and apoptosis represent morphologic
expressions of a shared biochemical network described as the
“apoptosis-necrosis continuum” (Zeiss, 2003).

Radiation vaccine.
• Whether a cell dies by necrosis or apoptosis depends in part on the
nature of the cell death signal, the tissue type, the developmental
stage of the tissue and the physiologic milieu (Fiers et al., 1999; Zeiss,
2003).
• Interesting.

Radiation vaccine.
• Necrosis is an uncontrolled and passive process that usually affects
large fields of cells whereas apoptosis is controlled and energy-
dependent and can affect individual or clusters of cells. Necrotic cell
injury is mediated by two main mechanisms; interference with the
energy supply of the cell and direct damage to cell membranes.
• Apoptosis: A Review of Programmed Cell Death SUSAN ELMORE NIEHS,
Laboratory of Experimental Pathology, Research Triangle Park, North Carolina
27709, USA
• http://tpx.sagepub.com/content/35/4/495.full.pdf+html

Radiation vaccine.
• Some of the major morphological changes that occur with necrosis
include cell swelling; formation of cytoplasmic vacuoles; distended
endoplasmic reticulum; formation of cytoplasmic blebs; condensed,
swollen or ruptured mitochondria; disaggregation and detachment of
ribosomes; disrupted organelle membranes; swollen and ruptured
lysosomes; and eventually disruption of the cell membrane (Kerr et
al., 1972; Majno and Joris, 1995; Trump et al., 1997)

Radiation vaccine.
• This loss of cell membrane integrity results in the release of the
cytoplasmic contents into the surrounding tissue, sending chemotatic
signals with eventual recruitment of inflammatory cells. Because
apoptotic cells do not release their cellular constituents into the
surrounding interstitial tissue and are quickly phagocytosed by
macrophages or adjacent normal cells, there is essentially no
inflammatory reaction (Savill and Fadok, 2000; Kurosaka et al., 2003).

Radiation vaccine.
• Until recently, apoptosis has traditionally been considered an
irreversible process with caspase activation committing a cell to death
and the engulfment genes serving the purpose of dead cell removal.
However, the uptake and clearance of apoptotic cells by macrophages
may involve more than just the removal of cell debris. Hoeppner et al.
have shown that blocking engulfment genes in C. elegans embryos
enhances cell survival when cells are subjected to weak pro-apoptotic
signals (Hoeppner et al., 2001).

Radiation vaccine.
• Some research suggests that DNA repair is activated early in the p53-
induced apoptotic process and that this DNA repair may be involved
in reversing the cell death pathway in some circumstances.

Radiation vaccine.
• The mechanisms of apoptosis are highly complex and sophisticated,
involving an energy-dependent cascade of molecular events . To date,
research indicates that there are two main apoptotic pathways: the
extrinsic or death receptor pathway and the intrinsic or mitochondrial
pathway. However, there is now evidence that the two pathways are
linked and that molecules in one pathway can influence the other
(Igney and Krammer, 2002).
•

Radiation vaccine.
• There is an additional pathway that involves T-cell mediated
cytotoxicity and perforin-granzyme-dependent killing of the cell. The
perforin/granzyme pathway can induce apoptosis via either granzyme
B or granzyme A. The extrinsic, intrinsic, and granzyme B pathways
converge on the same terminal, or execution pathway. This pathway is
initiated by the cleavage of caspase-3 and results in DNA
fragmentation, degradation of cytoskeletal and nuclear proteins,
cross-linking of proteins, formation of apoptotic bodies, expression of
ligands for phagocytic cell receptors and finally uptake by phagocytic
cells. The granzyme A pathway activates a parallel, caspase-
independent cell death pathway via single stranded DNA damage
(Martinvalet et al., 2005).

Radiation vaccine.
• Apoptotic cells exhibit several biochemical modifications such as
protein cleavage, protein cross-linking, DNA breakdown, and
phagocytic recognition that together result in the distinctive
structural pathology described previously (Hengartner, 2000).

Radiation vaccine.
• Caspases are widely expressed in an inactive proenzyme form in most
cells of plants and mammals, and once activated can often activate
other pro-caspases, allowing initiation of a protease cascade.
• This proteolytic cascade, in which one caspase can activate other
caspases, amplifies the apoptotic signaling pathway and thus leads to
rapid cell death.

irradiation.
• Programmed cell death (PCD) occurs in animals and plants under
various stresses and during development. Recently, vacuolar
processing enzyme (VPE) was identiﬁed as an executioner of plant
PCD.
• “A cellular suicide strategy of plants: vacuole-mediated cell death”
• Apoptosis 2006; 11: 905–911 C 2006 Springer Science + Business
Media, LLC. Manufactured in The United States. DOI:
10.1007/s10495-006-6601-1. N. Hatsugai et al.

irradiation.
• Recently, vacuolar processing enzyme (VPE) was identiﬁed as an
executioner of plant PCD. VPE is a cysteine protease that cleaves a
peptide bond at the C-terminal side of asparagine and aspartic acid.
• “A cellular suicide strategy of plants: vacuole-mediated cell death”
• Apoptosis 2006; 11: 905–911 C 2006 Springer Science + Business
Media, LLC. Manufactured in The United States. DOI:
10.1007/s10495-006-6601-1. N. Hatsugai et al.

irradiation.
• Programmed cell death (PCD) is an active, genetically controlled
• process leading to selective elimination of unwanted or damaged cells
in eukaryotes. PCD is essential for growth and development of
multicellular organisms as well as for proper response to environment
(Gechev et al., 2006; Lam, 2004).

irradiation.
• Plant PCD is associated with a number of developmental processes
including embryo formation, degeneration of the aleurone layer
during monocot seed germination, differentiation of tracheary
elements in water-conducting xylem tissues, formation of root
aerenchyma and epidermal trichomes, anther tapetum degeneration,
floral organ abscission, pollen self-incompatibility, remodeling of
some types of leaf shape, and leaf senescence. (Gechev et al., 2006;
Thomas and Franklin-Tong, 2004).
• Programmed Cell Death in Plants: New Insights into Redox Regulation
• and the Role of Hydrogen Peroxide
• Ilya Gadjev,1,* Julie M. Stone,† and Tsanko S. Gechev*

irradiation.
• Hydrogen peroxide (H2O2) and other reactive oxygen species (ROS)
have become recognized to be key modulators of PCD of as well as
many other biological processes such as growth, development, and
stress adaptation (Gechev et al., 2006).

irradiation.
• Although specific ROS receptors/sensors remain largely elusive,
downstream components of H2O2 and ROS signal transduction
networks controlling plant PCD have been identified, including
protein kinases, protein phosphatases, and transcription factors. The
majority of these are restricted to plants, with only a few genes
having close homologues in animals. (Gechev et al., 2006).

irradiation.
• Hydrogen peroxide is produced in all cellular compartments as a
result of reactions of energy transfer, electron leakage from saturated
electron transport chains, and the activities of various oxidases and
peroxidases (Apel and Hirt, 2004).

irradiation.
• Programmed cell death (PCD) is a process by which cells in many
organisms die. The basic morphological and biochemical features of
PCD are conserved between the animal and plant kingdoms.
Cysteine proteases have emerged as key enzymes in the regulation of
animal PCD.

irradiation.
• The discovery that cell death is a tightly regulated (programmed)
process has stirred a great deal of interest in its mechanisms.
Studies of animal systems have shown that the execution of
programmed cell death (PCD) or apoptosis is controlled by a multistep
signaling pathway (McConkey and Orrenius, 1994; Stewart, 1994).
• In plants, PCD has been implicated in xylogenesis (Fukuda,
1996; Groover et al., 1997), in some forms of senescence,
and in the hypersensitive response to pathogens and environmental
stresses (Greenberg, 1996; Mittler and Lam,
1996; Lamb and Dixon, 1997).

irradiation.
• Although a detailed understanding of how plant cells die is still largely
unknown, recent studies have shown that the apoptotic pathways of
the animal and plant kingdoms are morphologically and biochemically
similar (Greenberg, 1996; Levine et al., 1996; Wang et al., 1996).

irradiation.
• Specifically, the morphological hallmarks of apoptosis include
cytoplasmic shrinkage, nuclear condensation, and membrane
blebbing (Earnshaw, 1995; Martins and Earnshaw, 1997); the
biochemical events involve calcium influx, exposure of
phosphatidylserine and activation of specific proteases and DNA
fragmentation, first to large 50-kb fragments and then to nucleosomal
ladders (McConkey and Orrenius, 1994; Stewart, 1994; Wang et al.,
1996; O’Brien et al., 1998).

irradiation.
• The Involvement of Cysteine Proteases and Protease Inhibitor Genes in the
Regulation of Programmed Cell Death in Plants.
• The Plant Cell, Vol. 11, 431–443, March 1999, www.plantcell.org © 1999
American Society of Plant Physiologists.

irradiation.
• VPE processing system mediates a cellular suicide strategy in plants. In
animals, dying cells are packaged into apoptotic bodies
• and then engulfed by phagocytes. In contrast, because plants do not have
phagocytes and the cells are surrounded by rigid cell walls, plant
• cells must degrade their materials by themselves. VPE, which has caspase-
1-like activity, is accumulated after perception of death signals such
• as pathogen infection. VPE is involved in activation of the target proteins to
provoke disintegration of the vacuolar membranes. Consequently,
• the vacuolar hydrolytic enzymes leave the vacuole for the cytosol and
degrade cellular components. Plants have evolved a death strategy that
• is mediated by the VPE processing system, which is not seen in animals.
A cellular suicide strategy of plants: vacuole-mediated cell death.
N. Hatsugai et al. DOI: 10.1007/s10495-006-6601-1

irradiation.
• The genome of an organism is under constant attack from endogenous and
exogenous DNA damaging factors, such as reactive radicals, radiation, and
genotoxins. Therefore, DNA damage response systems to sense DNA
damage, arrest cell cycle, repair DNA lesions, and/or induce programmed
cell death are crucial for maintenance of genomic integrity and survival of
the organism. Genome sequences revealed that, although plants possess
many of the DNA damage response factors that are present in the animal
systems, they are missing some of the important regulators, such as the
p53 tumor suppressor. These observations suggest differences in the DNA
damage response mechanisms between plants and animals. In this review
the DNA damage responses in plants and animals are compared and
contrasted. In addition, the function of SUPPRESSOR OF GAMMA
RESPONSE 1 (SOG1), a plant-specific transcription factor that governs the
robust response to DNA damage, is discussed.
Biology 2013, 2, 1338-1356; doi:10.3390/biology2041338

irradiation.
• Can irradiated plant’s cells used for feeding induce radiation disease
of mammals?
• Yes.

irradiation.
• A careful analysis by FDA of all Army data present (including 31 loose-
leaf notebooks of animal feeding test results) showed significant
adverse effects produced in animals fed irradiated food...
• http://www.mercola.com/article/irradiated/irradiated_research.htm
• In the course of legalizing the irradiation of beef, chicken, pork, fruit,
vegetables, eggs, juice, spices and sprouting seeds -- a process that
has spanned nearly 20 years -- the U.S. Food and Drug Administration
has dismissed or ignored a substantial body of evidence suggesting
that irradiated food may not be safe for human consumption.

irradiation.
• What were these adverse effects?
• A decrease of 20.7 percent in surviving weaned rats.
• A 32.3 percent decrease in surviving progeny of dogs.
• Dogs weighing 11.3 percent less than animals on the control diets...
Carcinomas of the pituitary gland, a particularly disturbing finding
since this is an extremely rare type of malignant tumor."
• Food irradiation: An FDA report. FDA Papers, Oct. 1968.

irradiation.
• Fatal Internal Bleeding in Rats (I)
• "A significant number of rats consuming irradiated beef died from
internal hemorrhage within 46 days, the first death of a male rat
coming on the 11th day of feeding. This rat became sluggish on the
8th day of the regimen and started refusing food. He continued to be
morbid during the next two days, did not eat any food, lost weight
and appeared anemic. He was found dead on the 11th day.
• Vitamin K deficiency in rats induced by feeding of irradiated beef.
• Journal of Nutrition, 69:18-21, 1959. (Cosponsored by the Surgeon
General of the US Army)

irradiation.
• Fatal Internal Bleeding in Rats (II)
• "Hemorrhagic death had occurred in all males fed irradiated diets by
day 34... There is evidence to suggest that inefficient absorption of
vitamins, i.e. vitamin K, from the intestinal tract may contribute to a
deficiency state." [Note: Vitamin K plays a major role in blood
clotting.]
• Influence of age, sex, strain of rat and fat soluble vitamins on
hemorrhagic syndromes in rats fed irradiated beef.
• Federation Proceedings, 19:1045-1048, 1960. (Cosponsored by the
Surgeon General of the US Army)

irradiation.
• Fetal Deaths in Mice
• "Freshly irradiated diets produced elevated levels of early deaths in
[mice fetuses]... The increase in early deaths would suggest that the
diet when irradiated has some mutagenic potential."
• Irradiated laboratory animal diets: Dominant lethal studies in the
mouse.
• Mutation Research, 80:333-345, 1981.

irradiation.
• Toxic effects of irradiated foods. Nature, 211:302, 1966.
• A Thalidomide Warning (II)
• "Irradiating can bring about chemical transformations in food and food
components resulting in the formation of potential mutagens, particularly
hydrogen peroxide and various organic peroxides.
• It is now realized, especially since the thalidomide episode, that older
testing protocols do not detect the more subtle population hazards such as
mutagens and teratogens. In view of the serious consequences to the
human population which could arise from a high level of induced
mutations, it is desirable that protocols for irradiated food should include
in vivo tests on mammals for possible mutagenicity."
• Mutagenicity and cytotoxicity of irradiated foods and food components.

irradiation.
• Bulletin of the World Health Organization, 41:873-904,
1969. (Cosponsored by the US Atomic Energy Commission and Food and
Drug Administration)
• A Host of Problems
• "Numerous studies have been carried out to ascertain whether cytotoxic
effects occur when un irradiated biological test systems are cultured or fed
with irradiated media or food. In such studies, adverse physiological
growth retardation and inhibition, cytological cell division inhibition and
chromosome aberrations and genetical effects have been observed in a
wide range of test systems, ranging from bacteriophages to human cells...
The available data suggest that a variety of free radicals may act as the
toxic and mutagenic agents.“

irradiation.
• Cytotoxic and mutagenic effects of irradiated substrates and food
material. Radiation Botany, 11:253-281, 1971.
• A Cancer Warning
• "An increase in concentration of a mutagen in food by irradiation
will increase the incidence of cancer. It will take four to six decades to
demonstrate a statistically significant increase in cancer due to
mutagens introduced into food by irradiation. When food irradiation
is finally prohibited, several decades worth of people with increased
cancer incidence will be in the pipeline.“

irradiation.
• Growth, reproduction, survival and histopathology of rats fed beef
irradiated with electrons. Food Research, 20:193-214, 1955.
• Chromosomal Damage to Human Cells (I)
• "Irradiated sucrose solutions were extremely toxic to human white
blood cells. Cell divisions were inhibited. Degenerated cell divisions
were observed and the chromosomes were grossly damaged. The
DNA was clumped or the chromosomes appeared shattered or
pulverized. In contrast, treatment with un irradiated sucrose at the
same concentration had no apparent effect on the mitotic rate and
the chromosomes were not visibly damaged.“

irradiation.
• Cytotoxic and radiomimetic activity of irradiated culture medium on
human leukocytes. Current Science, 16:403-404, 1966.
• Toxic Chemical Formed in Food Containing Fat (I)
• "When food containing fat is treated by ionizing radiation, a group of
2-alkylcyclobutanones [toxic chemicals] is formed. To date, there is no
evidence that the cyclobutanones occur in unirradiated food. In vitro
experiments using rat and human colon cells indicate that 2-
dodecylcyclobutanone (2-DCB)... is clearly cytotoxic and genotoxic.“

irradiation.
• Radiation Toxins – Effects of Radiation Toxicity, Molecular
Mechanisms of Action, Radiomimetic Properties and Possible
Countermeasures for Radiation Injury.
• http://www.intechopen.com/books/current-topics-in-ionizing-
radiation-research/radiation-toxins-molecular-mechanisms-of-
toxicity-and-radiomimetic-properties-

irradiation.
• Some results under way.

irradiation.

Radiation protection: Anti Radiation Vaccine Technology.

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