Carcinogenicity
Carcinogenicity refers to a process where carcinogenic
substances induce (malignant) tumours, increase their incidence or malignancy,
or shorten the time of tumour occurrence after inhalation, ingestion, dermal
application or injection. It is generally accepted that carcinogenesis is a
multihit/ multi-step process from the transition of normal cells into cancer
cells via a sequence of stages and complex biological interactions, strongly
influenced by factors such as genetics, age, diet, environment, hormonal
balance, etc.
substances induce (malignant) tumours, increase their incidence or malignancy,
or shorten the time of tumour occurrence after inhalation, ingestion, dermal
application or injection. It is generally accepted that carcinogenesis is a
multihit/ multi-step process from the transition of normal cells into cancer
cells via a sequence of stages and complex biological interactions, strongly
influenced by factors such as genetics, age, diet, environment, hormonal
balance, etc.
Carcinogenicity can be divided into two categories
according to their presumed mode of action: genotoxic carcinogens and
non-genotoxic carcinogens.
according to their presumed mode of action: genotoxic carcinogens and
non-genotoxic carcinogens.
Genotoxic
carcinogens
carcinogens
They have the ability to interact with DNA and/or
the cellular apparatus (such as e.g.
the spindle apparatus and topoisomerase enzymes) and thereby affect
the integrity of the genome,
the cellular apparatus (such as e.g.
the spindle apparatus and topoisomerase enzymes) and thereby affect
the integrity of the genome,
Non-genotoxic
carcinogens
carcinogens
They exert their carcinogenic effects through other
mechanisms that do not involve direct alterations in DNA. The complexity of the
carcinogenicity process makes it difficult to develop in vitro alternative test models that mimic the full process,
especially for non-genotoxic chemicals.
mechanisms that do not involve direct alterations in DNA. The complexity of the
carcinogenicity process makes it difficult to develop in vitro alternative test models that mimic the full process,
especially for non-genotoxic chemicals.
Mutagenesis
Mutagenesis
is the induction of genetic change in a cell by the alterations in the cell’s genetic material
(usually deoxyribonucleic acid [DNA]). If
the mutation
occurs in a gamete (sex cell), the genetic alteration may be passed
to subsequent generations. This change or alteration can subsequently be
inherited from one cell to the next. While many mutations are benign, some can
be detrimental and cause human genetic disease. Mutations provide a mechanism for evolution
if the mutations in the DNA produce a new or modified protein that has enhanced
or new beneficial functions such that this newly acquired characteristic has a
selective survival advantage and thus will be more likely to be passed down
from one generation to the next. However, there are cells which will not have
the potential to develop into any other cell types because they are usually
spontaneous and not inherited. This is as a result of mutations in somatic
cells, or cells that have undergone differentiation
is the induction of genetic change in a cell by the alterations in the cell’s genetic material
(usually deoxyribonucleic acid [DNA]). If
the mutation
occurs in a gamete (sex cell), the genetic alteration may be passed
to subsequent generations. This change or alteration can subsequently be
inherited from one cell to the next. While many mutations are benign, some can
be detrimental and cause human genetic disease. Mutations provide a mechanism for evolution
if the mutations in the DNA produce a new or modified protein that has enhanced
or new beneficial functions such that this newly acquired characteristic has a
selective survival advantage and thus will be more likely to be passed down
from one generation to the next. However, there are cells which will not have
the potential to develop into any other cell types because they are usually
spontaneous and not inherited. This is as a result of mutations in somatic
cells, or cells that have undergone differentiation
A
single nucleotide change, called a point mutation, can cause a genetic disease
if it occurs in a gene important for normal cellular function. Deletions
involve deleted sequence of DNA that can be in a coding gene sequence (called
an exon) or a noncoding sequence of the gene (called an intron) or the
noncoding sequence that separates genes. Deletions can be in a single
nucleotide or span several genes. There is a repeat sequence of DNA referred to
as DNA duplications. Alteration of an individual gene, or a specific letter in the DNA alphabet called a
nucleotide can result from mutagenesis. There are four nucleotides, adenine,
guanine, cytosine, and thymine. Mutagenesis—or the process acquiring
mutations—can be in the form of a point mutation, a deletion, or a duplication
in the DNA sequence.
single nucleotide change, called a point mutation, can cause a genetic disease
if it occurs in a gene important for normal cellular function. Deletions
involve deleted sequence of DNA that can be in a coding gene sequence (called
an exon) or a noncoding sequence of the gene (called an intron) or the
noncoding sequence that separates genes. Deletions can be in a single
nucleotide or span several genes. There is a repeat sequence of DNA referred to
as DNA duplications. Alteration of an individual gene, or a specific letter in the DNA alphabet called a
nucleotide can result from mutagenesis. There are four nucleotides, adenine,
guanine, cytosine, and thymine. Mutagenesis—or the process acquiring
mutations—can be in the form of a point mutation, a deletion, or a duplication
in the DNA sequence.
The
major cause of mutagenesis is due to exposure to ionizing radiation
and certain chemicals. Ionizing radiations include cosmic rays, x rays, and ultraviolet light. It is of interest to note that melanoma, caused
almost exclusively by exposure to the ultraviolet radiation
from the sun, is the most rapidly increasing lethal cancer in the world. In melanoma, ultra violet radiation
induces what is called thymine dimers. This means that two thymine nucleotides
next to each other in a DNA sequence form an abnormal bond. Thymine dimers in a
skin cell can lead to skin cancer. The depletion of ozone layer and consequent
increased exposure of ultraviolet radiation of the skin heightened prevalence
of melanoma
major cause of mutagenesis is due to exposure to ionizing radiation
and certain chemicals. Ionizing radiations include cosmic rays, x rays, and ultraviolet light. It is of interest to note that melanoma, caused
almost exclusively by exposure to the ultraviolet radiation
from the sun, is the most rapidly increasing lethal cancer in the world. In melanoma, ultra violet radiation
induces what is called thymine dimers. This means that two thymine nucleotides
next to each other in a DNA sequence form an abnormal bond. Thymine dimers in a
skin cell can lead to skin cancer. The depletion of ozone layer and consequent
increased exposure of ultraviolet radiation of the skin heightened prevalence
of melanoma
Tumour
suppressor genes can be affected by mutation resulting in uncontrollable
cellular growth, also called cancer. If this cancer is not detected early and
removed, it can become vascularized and leak into the bloodstream. If it
metastizes in this way, the cancer can quickly spread to other organs.
Additionally, a number of chemicals have been identified as mutagenic such as
the common household cleaner bleach. Many chemicals intercalate into the DNA double helix
and cause errors during DNA replication.
Chemicals that bind to DNA are called DNA adducts. Mutagenesis is induced by
many environmental carcinogens or cancer-causing chemicals
suppressor genes can be affected by mutation resulting in uncontrollable
cellular growth, also called cancer. If this cancer is not detected early and
removed, it can become vascularized and leak into the bloodstream. If it
metastizes in this way, the cancer can quickly spread to other organs.
Additionally, a number of chemicals have been identified as mutagenic such as
the common household cleaner bleach. Many chemicals intercalate into the DNA double helix
and cause errors during DNA replication.
Chemicals that bind to DNA are called DNA adducts. Mutagenesis is induced by
many environmental carcinogens or cancer-causing chemicals
One
mechanism, called nucleotide excision repair, involves recognition and removal
of damaged DNA by nicking it where there is a point mutation, removing the
damaged nucleotide sequence, re-synthesis to add the correct nucleotide, and
DNA ligation of the nicked DNA to seal the DNA where it is being repaired. Despite
the many different ways that mutagenesis can occur, mechanisms for DNA repair
exist that help maintain the integrity of the genome.
mechanism, called nucleotide excision repair, involves recognition and removal
of damaged DNA by nicking it where there is a point mutation, removing the
damaged nucleotide sequence, re-synthesis to add the correct nucleotide, and
DNA ligation of the nicked DNA to seal the DNA where it is being repaired. Despite
the many different ways that mutagenesis can occur, mechanisms for DNA repair
exist that help maintain the integrity of the genome.
Reproductive
toxicology
toxicology
Reproductive
toxicology can be referred to as the toxic effects of various substances on
reproductive ability of an organism. In other words it can also be called as
developmental toxicology. This is toxicity of chemicals on fertility and sexual
function of organism. This can be due to exposure of hazardous substances
during prenatal period. It is a special part of toxicology which comprises any
effect of chemicals and active substances on mammalian reproduction (fertility,
weaning) and development (embryonal and fetal development).
toxicology can be referred to as the toxic effects of various substances on
reproductive ability of an organism. In other words it can also be called as
developmental toxicology. This is toxicity of chemicals on fertility and sexual
function of organism. This can be due to exposure of hazardous substances
during prenatal period. It is a special part of toxicology which comprises any
effect of chemicals and active substances on mammalian reproduction (fertility,
weaning) and development (embryonal and fetal development).
Several
methods are used to determine the reproductive toxicity of various substances.
The major test is developmental toxicity screening assay. The investigations
and the interpretation of the results should be related to all other
pharmacological and toxicological data available to determine the risk of the
test compound to humans. Observations of this are best measured in a close
study of all stages of development from conception of one generation to
conception of the following generation(s) to allow detection of immediate and
latent effects of exposure which covers one complete life cycle from the mature
adult.
methods are used to determine the reproductive toxicity of various substances.
The major test is developmental toxicity screening assay. The investigations
and the interpretation of the results should be related to all other
pharmacological and toxicological data available to determine the risk of the
test compound to humans. Observations of this are best measured in a close
study of all stages of development from conception of one generation to
conception of the following generation(s) to allow detection of immediate and
latent effects of exposure which covers one complete life cycle from the mature
adult.
References
David,
L. (2002). Emery and Rimoin’s Principles and Practice of Medical Genetics.
London; New York: Churchill Livingstone.
L. (2002). Emery and Rimoin’s Principles and Practice of Medical Genetics.
London; New York: Churchill Livingstone.
Robert,
L. Nussbaum, R & McInnes, F. (2001). Genetics in Medicine.
Philadelphia: Saunders.
L. Nussbaum, R & McInnes, F. (2001). Genetics in Medicine.
Philadelphia: Saunders.
(2009) Developmental
toxicity testing of monoclonal antibodies: an enhanced pre- and postnatal study
design option. Reprod Toxicol 28:
220-225.
toxicity testing of monoclonal antibodies: an enhanced pre- and postnatal study
design option. Reprod Toxicol 28:
220-225.
