amino groups of tissue protein, forming thiocarbamate and thiazolidone,
which might form soluble chelate with Zn.
12
It has been suggested that metal chelation may be one of the mechanisms
involved in carcinogenesis. Many carcinogens have, or can be metabolized to,
chemical species capable of metal-binding. This in turn may aid the entrance of
metals into cells. Once inside the cells, interaction between normal metals and
abnormal metals may occur, resulting in alteration of cellular metabolism.
4.4.4.4 Metal shift
The phenomenon called metal shift may account for some of the responses seen
in animals that are exposed to certain toxicants. Metal shift refers to movement
of metals from one organ to another due to the presence of a toxicant, and is
among the earliest biological indicators of toxic response. For example, rats
exposed to F show an increase in serum Zn content, whereas the levels of Se
and Al in the rats’ whiskers were decreased.
13 A similar change was observed
with rats exposed to O 3 . When exposed to O 3 for 4 hours, the rats showed
increased levels of Cu, Mo, and Zn in their lungs, while the levels of these
metals in the liver were decreased.
4.4.5 FREE-RADICAL-MEDIATED REACTIONS
A free radical is any molecule with an odd number of electrons, and can occur
as both organic and inorganic molecules. Free radicals are highly reactive and
therefore highly unstable and short-lived. For instance, the half-life of lipid
peroxyl radical (ROO
Á ) is 7 seconds, and that of hydroxyl radical (HO
Á ) is
10
À9 seconds
Free radicals are derived from both natural and anthropogenic sources.
They are produced naturally in vivo as byproducts from normal metabolism.
Some of the examples include superoxide free radical (O 2
Á À ) and H 2 O 2 .
Anthropogenic sources of free radicals are found in such situations as when an
organism is exposed to ionizing radiation, certain drugs, or various xenobiotics. The free radicals thus produced can cause chain reactions and damage
critical cellular constituents, including proteins, lipids, and DNA. In proteins,
the consequence of free-radical attacks is manifested by peptide-chain scission
and denaturation. With DNA, strand scission or base modification may occur,
potentially leading to cell mutation and death. Researchers generally agree that
many human diseases, including heart disease and certain types of cancer, are
attributable, at least partly, to free-radical-mediated reactions.
As free radicals react with the unsaturated fatty acids and cholesterol, such
as those in cellular membranes, they can induce lipid peroxidation. This
process, in turn, can become autocatalytic after initiation, leading to the
production of lipid peroxide, lipid alcohol, aldehydes and other chemical
species.
14 Interaction with other cellular constituents can also occur, thus
injuring cells. Obviously, by inducing these reactions, free radicals can damage
cell plasma membranes, and those of organelles.
Toxic Action of Pollutants
59
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-004.3d]
Ref: 4365 MING-HO YU Chap-004 Page: 59 45-64
which might form soluble chelate with Zn.
12
It has been suggested that metal chelation may be one of the mechanisms
involved in carcinogenesis. Many carcinogens have, or can be metabolized to,
chemical species capable of metal-binding. This in turn may aid the entrance of
metals into cells. Once inside the cells, interaction between normal metals and
abnormal metals may occur, resulting in alteration of cellular metabolism.
4.4.4.4 Metal shift
The phenomenon called metal shift may account for some of the responses seen
in animals that are exposed to certain toxicants. Metal shift refers to movement
of metals from one organ to another due to the presence of a toxicant, and is
among the earliest biological indicators of toxic response. For example, rats
exposed to F show an increase in serum Zn content, whereas the levels of Se
and Al in the rats’ whiskers were decreased.
13 A similar change was observed
with rats exposed to O 3 . When exposed to O 3 for 4 hours, the rats showed
increased levels of Cu, Mo, and Zn in their lungs, while the levels of these
metals in the liver were decreased.
4.4.5 FREE-RADICAL-MEDIATED REACTIONS
A free radical is any molecule with an odd number of electrons, and can occur
as both organic and inorganic molecules. Free radicals are highly reactive and
therefore highly unstable and short-lived. For instance, the half-life of lipid
peroxyl radical (ROO
Á ) is 7 seconds, and that of hydroxyl radical (HO
Á ) is
10
À9 seconds
Free radicals are derived from both natural and anthropogenic sources.
They are produced naturally in vivo as byproducts from normal metabolism.
Some of the examples include superoxide free radical (O 2
Á À ) and H 2 O 2 .
Anthropogenic sources of free radicals are found in such situations as when an
organism is exposed to ionizing radiation, certain drugs, or various xenobiotics. The free radicals thus produced can cause chain reactions and damage
critical cellular constituents, including proteins, lipids, and DNA. In proteins,
the consequence of free-radical attacks is manifested by peptide-chain scission
and denaturation. With DNA, strand scission or base modification may occur,
potentially leading to cell mutation and death. Researchers generally agree that
many human diseases, including heart disease and certain types of cancer, are
attributable, at least partly, to free-radical-mediated reactions.
As free radicals react with the unsaturated fatty acids and cholesterol, such
as those in cellular membranes, they can induce lipid peroxidation. This
process, in turn, can become autocatalytic after initiation, leading to the
production of lipid peroxide, lipid alcohol, aldehydes and other chemical
species.
14 Interaction with other cellular constituents can also occur, thus
injuring cells. Obviously, by inducing these reactions, free radicals can damage
cell plasma membranes, and those of organelles.
Toxic Action of Pollutants
59
[16:54 26/8/04 P:/CRC PRESS/4365 MING-HO.751 (1670)/4365-004.3d]
Ref: 4365 MING-HO YU Chap-004 Page: 59 45-64