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Radiation can affect the body in a number of ways and harmful health consequences may not be
seen for many years (NA, 2002). Effects are dependent on the type of radiation, the route of
exposure(s), the length of time a person is exposed and the amount of radiation absorbed by
the body (the dose). Effects can be mild, such as reddening of the skin, or as serious as
cancer and even death (NA, 2004). There are both short- and long-term effects of
radiation, which can increase the risk of cancer. If a reasonable dose estimate can be
made, a lot is known about the health effects at that dose. Uses of radiation. Our
hospitals, military and public, depend on the use of radioactive materials for
electricity, medical diagnosis and treatment, research, manufacturing processes and
munitions (see Table 1). The widespread use of radioactive materials brings with it the
equally widespread possibility for accidental or intentional exposure. These materials can
be used to create a Radioactive Dispersal Device (RDD) but the greater concern is one of
accidental inhalation, ingestion, or absorption through a wound.
Effects of ionizing radiation on living matter. Deoxyribonucleic acid (DNA) is
the key factor in the biological effects of ionizing radiation (Terato, Tanaka, Nakaarai,
Furusawa, & Ide, 2004). Radiation induces DNA damage by reactive oxygen species (ROS)
resulting from the ionization of water (Terato et al., 2004). This is similar to ROS damage
from normal aerobic metabolism. There are some repair mechanisms for DNA damage. If
survives it can result in malignant diseases such as carcinogenesis (Terato et al.,
2004). The simplest effect that ionizing radiation has on the cell is apoptosis.
Non-lethal changes that occur at lower doses include: a) delayed mitosis causing changes
in cell kinetic patterns, b) disruptions in cell growth, c) increased or decreased
permeability resulting from a change in the lipid bilayers resulting a loss of metabolic
equilibrium, and d) decreased cell motility (NATO, 2005). It follows that the cells most
sensitive to radiation are those that are actively proliferating. For example,
hemocytoblasts and lymphocytes are very sensitive to radiation. Likewise the cells that are
most radioresistant are those that do not normally divide, such as striated muscle cells.
Skeletal muscle is listed among the cells that are the least radiosensitive. Despite the
fact that skeletal is less radiosensitive than most cells there is evidence that it is
impacted. It has been shown that muscle cells exposed to low doses of ionizing radiation
loose the ability to generate passive and active tension in response to stretch and
calcium. This loss of stretch is believed to be the result of the depletion of titin and
nebulin (Horowits, Kempner, Bisher, & Podolsky, 1986).
Carcinogenesis can develop in any tisuee at any time and is a complex biological process that
is best viewed as a system. Armitage and Doll proposed a classic theory of cancer that
is considered foundational. Within that tissue there are a number of cells that can divide
and potentially experience a carcinogenic transformation. The kth change which is sudden
and irreversible results in the development of cancer.. The multistage model of
carcinogenesis serves as a foundation for hypothesis formation and the design of
experiments, especially in determining dose, age, and timing of administrations of
the suspected carcinogenic agent. The agent may serve as only one step in the
transformation of cells. The stages of carcinogenesis can be broken down into three stages:
initiation, promotion, and progression with each stage potentially having multiple
genetic changes. Initiation begins the process by the irreversible alteration of
cells. Promotion occurs when the altered cell expands to become a visible tumor.
Progression is considered the time when tumors move from benign to malignant . This
process can be used to explain how a noncarciongenic agent can influence the carcinogenic
process, such as is the case with much shrapnel.
Mitotic figures are present more frequently in cancer. They are counted in 10 consecutive HPFs
closest to the tumor.
Mitotic figures were counted near the pellet site in rats that did not have tumors. Ta
(n=12; mean 0 SEM +/-0) had no mitotic figures, whereas Ni (n=6, 21.67 +/- 11.67) was
significantly greater. WA low dose had more mitotic figures (13, 18.5, and 21.83) at 1, 3,
and 6 months than did WA high dose ( 2.5, 1.6, and 8.5) (Table 1) and even more than
Ni. H&E muscle sections showing areas of high
indicate mitotic cells. Panel A: Ni group, 6 months postimplantation. Panel B: WA
high-dose group, 6 months postimplantation. Panel C: WA low-dose group, 3 months
postimplantation. Panel D: Tissue section from WA low-dose group showing location of a Ta
pellet and a tungsten alloy (HMTA) pellet. Note the developing neoplastic area
surrounding the tungsten alloy pellet.
The neoplastic regions in the WA animals showed areas of increased invasion of muscle
tissue by the neoplastic cells often separating the individual fibers. This occurred to a
lesser extent with Ni. H&E staining of muscle tissue for rats implanted with metal
pellets for 6 month. Panel A: Tantalum. Panel B: Nickel. Tissue adjacent to tumor with
infiltrates between muscle fibers and classic signs of apoptosis – shrinkage and
apoptotic bodies (black arrow). Panel C: WA- low dose. Panel D: WA-high dose. Necrosis.
The incidence of tumor necrosis was determined through histological examination of
cross sections of the tumor. Generally, tumors with greater than 20% necrotic area are
considered positive for tumor necrosis (16). The controls included 0% of Ta and 83% of Ni
subjects positive for necrosis. Overall, 50% of WA low and 35% of WA high were positive for
necrosis with both having increasing percentages of animals positive for necrosis
at each time point. Myofibers were counted as disintegrated if they have internal nuclei,
fiber vaculation, cell swelling, necrosis, and increased circularity (11). WA
low- and high and all Ni showed signs of disintegration while Ta did not. As early as 1
month, 11% of the WA low fibers showed signs of disintegration. WA high had a greater
percentage of disintegrating fibers at all time points than WA low; and by 6 months 78% of
all WA high fibers showed signs of disintegration.
Histologic sections of gastrocnemius muscle implanted with metals. A-E (H&E, 10x) at
one month post implantation. F (gomori trichrome, 10x) of Ni 6 months post implantation with
increased collagen formation. A, WA high dose at 1-month shows infiltrates in spaces between
the myofibers. B, WA low dose at one month shows fibers of widely varying sizes. C, Ta
control apparently normal. D, WA high dose 1- month with multiple vacuoles. E, WA
1-month shows extensive destruction of fibers close to the pellet site including
varying fiber size, internal nuclei, and areas of necrosis.
Gomori trichrome (10x) near pellet implantation site. A-C, Ta shows little collagen
formation. D-F, WA low dose shows extensive collagen formation as early as 1 month.
F-I, WA high dose show extensive collagen formation at 1 month.
characterize and identify fibrotic and dystrophic changes in the skeletal muscle tissue
gomori trichrome was used to stain the collagen blue-green and the muscle fibers red. The
Ta control showed minimal increases in the about of collagen present from 1 to 6
months. Interestingly, both the WA high and low dose groups showed notable changes by
1-month post implantation and prior to the development of tumors (Figure 2). However,
the changes were greater in the WA high dose group. Fibrous changes occurred to a greater
extent adjacent to the pellet implantation site and decreased with distance from the
implantation site. This is even significantly different from Ni controls, which do not
show this effect and with the exception of the neoplastic area show no significant
difference in collagen from Ta controls
Because there is a useful correlation between the number of mitotic figures and the
biological behavior of a tumor (9), the number of mitotic figures was counted in 10
consecutive high power fields (HPF) (Figure 2). Figures counted were near the outermost
edge of the tumor where it joins the muscle fibers because this area is considered to be
the most proliferative (28). The mitotic rate was determined using H&E staining (10).
Mitotic figures were counted near the pellet site in rats that did not have tumors. Ta
(n=12; mean 0 SEM +/-0) had no mitotic figures, whereas Ni (n=6, 21.67 +/- 11.67) was
significantly greater. WA low dose had more mitotic figures (13, 18.5, and 21.83) at 1, 3,
and 6 months than did WA high dose ( 2.5, 1.6, and 8.5) (Table 1) and even more than
Ni. H&E muscle sections showing areas of high
indicate mitotic cells. Panel A: Ni group, 6 months postimplantation. Panel B: WA
high-dose group, 6 months postimplantation. Panel C: WA low-dose group, 3 months
postimplantation. Panel D: Tissue section from WA low-dose group showing location of a Ta
pellet and a tungsten alloy (HMTA) pellet. Note the developing neoplastic area
surrounding the tungsten alloy pellet.