Tobacco and Public Health - TCSC Indonesia

Introduction
Chapter 5
Tobacco smoke carcinogens: Human
uptake and DNA interactions
Stephen S. Hecht
Tobacco products cause approximately 30 per cent of all cancer death in developed
countries (Peto et al. 1996; World Health Organization 1997). In spite of this, there are
over 1 billion smokers in the world (World Health Organization 1997). Exposure to
environmental tobacco smoke (ETS) is also a recognized cause of cancer (National
Cancer Institute 1999). Mortality from cancers caused by tobacco products—lung,
larynx, oral cavity, esophagus, pancreas, kidney, liver, bladder, stomach, and colon—
will continue to be significant in the foreseeable future (International Agency for
Research on Cancer 1986b; Doll 1996; Chao et al. 2000). We need to achieve a better
understanding of mechanisms of tobacco-induced cancer in humans in order to develop
new cancer prevention strategies.
Carcinogens form the link between nicotine addiction and lung cancer (Fig. 5.1)
(Hecht 1999). Nicotine is the reason people continue to smoke in spite of the
well-known adverse health effects of this habit. Nicotine is not a carcinogen. However,
the cigarette is a disastrous nicotine-delivery device because carcinogens accompany
nicotine in each puff. Although the dose of each carcinogen per cigarette is quite small,
the cumulative dose in a lifetime of smoking can be considerable. Carcinogens are
responsible for cancer induction by tobacco products.
In most cases, tobacco carcinogens require enzymatic processing (metabolic activation)
to reactive forms (electrophiles) that bind to DNA, forming covalent binding products
called DNA adducts (Fig. 5.1). There are competing detoxification processes which are
protective. DNA adducts are absolutely central to the carcinogenic process. They can
be removed by cellular repair mechanisms. But if they persist, miscoding can occur
during DNA replication, leading to permanent mutations. If the mutations occur in
critical regions of genes involved in regulation of growth, such as oncogenes or tumor
suppressor genes, normal cellular growth control mechanisms can be lost and,
ultimately, cancer can develop. The carcinogen dose depends on the amount of a
tobacco product that an individual may use, and the way in which he or she uses it.
Individuals differ in the extent to which they activate tobacco carcinogens metabolically