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Toxic chemicals can cause genetic damage. The genetic material of a cell consists of
genes, which exist in chromosomes. Genes and chromosomes contain the information
that tells the cell how to function and how to reproduce (form new cells).
Some chemicals may change or damage the genes or chromosomes. This kind of change,
or damage in a cell is called a mutation. Anything that causes a mutation is called a
mutagen. Mutations may affect the way the cell functions or reproduces. The mutations
can also be passed on to new cells that are formed from the damaged cell. This can lead
to groups of cells that do not function or reproduce the same way the original cell did
before the mutation occurred.
Some kinds of mutation result in cancer. Most chemicals that cause cancer also cause
mutations. However, not all chemicals that cause mutations cause cancer.
Tests for the ability of a chemical to cause a mutation take little time and are relatively
easy to perform. If testing shows a chemical to be a mutagen, additional testing must be
done to determine whether or not the chemical also causes cancer.
Exposure to chemical substances may affect your children or your ability to have
children. Toxic reproductive effects include the inability to conceive children (infertility
or sterility), lowered sex drive, menstrual disturbances, spontaneous abortions
(miscarriages), stillbirths, and defects in children that are apparent at birth or later in the
child’s development.
There is not enough information on the reproductive toxicity of most chemicals. Most
chemicals have not been tested for reproductive effects in animals. It is difficult to predict
risk in humans using animal data. There may be “safe” levels of exposure to chemicals
that affect the reproductive system. However, trying to determine a “safe” level is very
difficult, if not impossible. It is even more difficult to study reproductive effects in
humans than it is to study cancer. At this time, only a few industrial chemicals are known
to cause birth defects or other reproductive effects in humans.1
CHROMOSOMAL ABBERATION
INTRODUCTION
Chromosomes are the organized form of DNA found in cells. Chromosomes contain one
very long, continuous piece of DNA, which contains many genes, regulatory elements
and other intervening nucleotide sequences. A broader definition of "chromosome" also
includes the DNA-bound proteins which serve to package and manage the DNA. The
word chromosome comes from the Greek (chroma, color) and (soma, body) due to their
property of being stained very strongly with vital and supravital dyes. 2,3
When an individual is missing either a chromosome from a pair (monosomy) or has more
than two chromosomes of a pair (trisomy). An example of a condition caused by
numerical abnormalities is Down Syndrome, also known as Trisomy 21 (an individual
with Down Syndrome has three copies of chromosome 21, rather than two). Turner
Syndrome is an example of monosomy, where the individual - in this case a female - is
born with only one sex chromosome, an X.
Structural Abnormalities:
When the chromosome's structure is altered. This can take several forms:
• Inversions: A portion of the chromosome has broken off, turned upside down and
reattached, therefore the genetic material is inverted.
• Rings: A portion of a chromosome has broken off and formed a circle or ring.
This can happen with or without loss of genetic material.
Most chromosome abnormalities occur as an accident in the egg or sperm. Therefore, the
abnormality is present in every cell of the body. Some abnormalities, however, can
happen after conception, resulting in mosaicism, where some cells have the abnormality
and some do not.
For purely pragmatic and diagrammatic purposes, we can regard the chromosomal
changes we see down the microscope as being the result of “breaks” followed by “re-
joins” of the chromosome thread. However, we must always remember that, in reality,
their origin is much more complicated
Since the chromosome we see and score at metaphase has two (sister-) chromatids, it is
convenient (and conventional) to divide all aberrations into two broad types:
Chromosome-type where the breaks and re-joins always affect both sister-chromatids at
any one locus. Examples in Figure 1.
Chromatid-type where the breaks and re-joins affect only one of the sister-chromatids at
any one locus (Fig 2
• If the breaks are situated in the arms of different (non-homologous or homologous)
chromosomes we have the category of INTERCHANGES.
• If the breaks are in the opposite arms of the same chromosome, we have the category
of INTER-ARM INTRACHANGES.
• If the two breaks are both in the same arm of a chromosome, we have the category of
INTRA-ARM INTRACHANGES.
These three categories are often referred to collectively as EXCHANGES.
• Finally, some aberrations appear to arise from a single, open break in just one arm.
This category we term “BREAKS” or “DISCONTINUITIES”. Many (perhaps all) of
them are, in reality, intra-arm intrachanges where one end has failed to join up
properly, though the limitations of microscopical resolution do not permit us to be
certain that the re-joining is really incomplete.5,6
Interaction between the four ends of two breaks can obviously take place in three
ways :
S-phase is a discrete period of interphase of a few hours duration during which the
chromosomal DNA and protein is duplicated, and the new chromatin segregated into the
sister-chromatids. Each chromosome has a precise programme of replication, closely
associated with its G-band pattern.
Pale G-bands always replicate early in S-phase, dark G-bands later, and constitutive
heterochromatin tends to be among the very last regions to replicate.
Most aberration-inducing agents can introduce lesions into the chromatin at all stages of
the cell cycle, but relatively few of them can produce actual structural changes in G1,(
and therefore give rise to primary chromosome-type changes) or in S and G2 (producing
primary chromatid-types,cobalt60 causes chromosome types of changes 10
Ionising radiation, restriction endonucleases, and a few chemicals like bleomycin and
some antibiotics are amongst those that can.
Any interference with or abnormality in the processes of chromatin replication also leads
to chromatid-type aberrations visible at next mitosis. It is almost certain that the vast
majority of “spontaneous” and de novo aberrations arise in this way. Chromosome
instability syndromes also probably produce aberrations via defective S-phase pathways.
However they are produced, the resulting chromatid-type aberrations are qualitatively
(but not quantitatively) identical
RECIPROCAL TRANSLOCATION
Reciprocal translocations (rcp) are among the most common constitutional chromosomal
aberrations in man. 11In a reciprocal translocation there is a mutual exchange of
chromosomal segments between two different chromosomes. This exchange can take
place between any two chromosomes and at various sites along the length of the
chromosome.12
PERICENTRIC INVERSION
An inversion in which the breakpoints occur on both arms of a chromosome. The inverted
segment spans the centromere.13 Pericentric inversion in chromosome 7 may play a role
in the etiology of the family's miscarriages 14
PARACENTRIC INVERSION
15
A chromosomal inversion that does not include the centromere. Very difficult to detect
at the chromosome level unless they are very large (many megabases of DNA). Again the
re-joining points can disrupt important genetic sequences, and reverse segments of the
reading frame. Large inversions will give problems at meiosis.
INTERSTITIAL DELETION
Deletion that does not involve the terminal parts of a chromosome called interstitial
deletion.16 A case of autism with an interstitial deletion on 4q leading to hemizygosity for
genes encoding for glutamine and glycine neurotransmitter receptor sub-units and
neuropeptide receptors 17
TERMINAL DELETION
Deletion is the loss of genetic material. . Terminal Deletion - a deletion that occurs
towards the end of a chromosome. Cryptic terminal deletion of chromosome 9q34 a novel
cause of syndromic obesity in childhood 18
Structural chromosome instability
An elevated frequency of structural chromosome aberrations could be directly caused by
an abnormally high incidence of DNA double-strand breaks. Chromosomal breakage can
result in a number of different structural rearrangements, some of which give rise to
abnormalities of chromosomal segregation at mitosis. For example, terminal deletions
due to a break of a single chromatid will result in a centric derivate chromosome plus an
acentric fragment. Because of its failure to bind the mitotic spindle, the fragment may be
permanently lost in the subsequent cell division, and may be seen as a lagging chromatin
body at metaphase or anaphase. Such lagging is a common finding in cell populations
exposed to ionising radiation .It has also been described in a number of solid tumours,
such as head and neck, and breast carcinomas .
Figure 1 Chromosome breakage-fusion-bridge (BFB) cycles: Dicentric (A) and ring (B)
chromosomes may form bridges at anaphase and the broken ends of the two chromatids
(red and white) may fuse into novel dicentric and ring-shaped structures in the daughter
cells.
Different mechanisms or steps in a single process
The common concurrence of BFB instability and centrosome abnormalities suggests that
these phenomena are mechanistically linked. Although it is true that both these
instabilities may be associated with similar molecular genetic lesions, such as TP53
mutation, their causal relationship, if any, remains unclear. There may be one rather
straightforward relationship, however. It is well established that anaphase bridging may
cause collapse of the cytokinetic process, leading to formation of cells with a duplicated
genome . Tumours with BFB events show a high frequency of binucleated cells . These
cells would not only carry the double amount of genetic material, but also twice the
normal number of centrosomes. After the next round of replication, such cells may thus
enter mitosis with abnormal centrosome configurations, leading to either tri- or tetrapolar
cell divisions (Figure 2). Incomplete cytokinesis could then easily explain the connection
between telomere shortening and BFB events, on one hand, and mitotic multipolarity, on
the other hand. 20
MUTAGEN
mutagen is a substance or agent that causes an increase in the rate of change in genes
(subsections of the DNA of the body's cells). These mutations (changes) can be passed
along as the cell reproduces, sometimes leading to defective cells or cancer.
Examples of mutagens include certain biological and chemical agents as well exposure to
ultraviolet light or ionizing radiation.Mutagenesis is the formation of mutations.
There are many types of mutations, some of which are harmful and others which have
little or no effect on the body's function..
ANTIMUTAGENIC HERBS
Mutagenic and antimutagenic properties of essential oil (EO) of basil and its major
constituent Linalool, reported to possess antioxidative properties 24
Mucuna collettii Lace is a Thai herb with a long record of consumption among mature
Thai males for the promotion of sexual potency proved to have antimutagenic potential.26
Anacardium occidentale L. species, popularly known as the cashew, which has several
therapeutic indications, such as cicatrizing, antihypertensive, hypoglycemic and
antitumoral properties proved to have antimutagenic activity.27
The major food items of Indian cuisine include rice, wheat, diary products, and abundant
fruits and vegetables. Beside these, there are several kinds of herbs and spices as
important ingredients, containing many phytochemicals with medicinal properties, adding
taste to Indian cuisine. An impressive body of data exists in support of the concept that
Indian food ingredients can be used in preventive strategies aimed at reducing the
incidence and mortality of different types of cancers because of their antioxidative,
antimutagenic and anticarcinogenic properties 28