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Current Knowledge on Lead as an Inducer of Human DNA Damage (pp. 265-285) $100.00
Authors:  (Joana Roma-Torres, Portuguese National Institute of Health, Centre of Environmental and Occupational Health, Portugal)
Abstract:
Since most ancient times lead has been widely used due to its physical and chemical
unique properties that make it an excellent metal with innumerable uses. Long ago
human kind has also found out about its adverse effects to health. Even so its utilisations
kept increasing exponentially alongside with industrialization and technology
improvements. Not until the two last decades of the 20th century has the earth begun to be
protected against its anthropogenic sources of widespread dissemination through
environmental systems. Steps taken in this direction are too important of a measure that
allows keeping its environmental concentrations essentially under control. Meanwhile
this may lead to the misconception that its total world production and use over the last
years has been diminishing, although real numbers point out to a constant increase [1, 2],
meaning there is still a huge number of people throughout the world exposed to it and,
consequently, to its toxic effects.
Lead is essentially a chronic or cumulative toxin, which can potentially affect every
organs and systems. International Agency for Research on Cancer (IARC) has classified
lead and inorganic lead compounds, back in 1987, as possibly carcinogenic in humans –
IARC group 2B [3], judging evidences to be inadequate in humans. IARC has however
undertaken a recent reevaluation of lead's carcinogenicity and changed that classification
to probably carcinogenic to humans – IARC group 2A [4] based in several studies that
concluded on a relationship between exposure to lead and cytogenetic markers
frequencies, such as micronucleus and chromosomal aberrations and on an increase of
incidence of overall cancer, and lung and bladder cancer [5, 6] in individuals exposed.
Genetic effects of lead seem to be mediated by modulation of reactive oxygen
species together with interaction with proteins, including those involved in DNA repair
in a way that can be considered indirect, by means of decreasing cells capability of
protecting and repairing damaged DNA in spite of directly damaging it [7]. Potential
genotoxic effects of lead might contribute for development of normal to cancerous cells
by inducing or allowing loss of genomic stability and acquisition of genetic alterations
[8, 9].
Within this chapter findings of genotoxicity in human populations and proposed
mechanisms for lead effects in genetic systems will be reviewed in order to obtain a state
of the art of such effects of lead in humans. 


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Current Knowledge on Lead as an Inducer of Human DNA Damage (pp. 265-285)