Smokeless "Spit" tobacco contains over 2,000

chemicals, many of which have been directly

related to causing cancer
• Tobacco can induce the development of oral
leukoplakia and erythroleukoplakia which
have a potential risk for malignant
transformation.
• Tobacco can induce cellular changes and
atypia typical of pre-malignant and frankly
malignant transformation.
• Tobacco contains carcinogenic agents.
• Tobacco seems to induce genetic mutation of
certain tumor suppressor genes and to co-
participate in cancer etiology by increasing the
over expression of such genes.
• 1. The scientific evidence is strong that the use of
smokeless tobacco can cause cancer in humans.
The association between smokeless tobacco use
and cancer is strongest for cancers of the oral
cavity, several times more frequently among snuff
dippers than among nontobacco users

• 2. Some investigations suggest that the use of

chewing tobacco also may increase the risk of oral
cancer.
• . Experimental investigations have revealed
potent carcinogens in snuff and chewing
tobacco.
• These include: nitrosamines,
• polycyclic aromatic hydrocarbons,

• radiation-emitting polonium.
• The tobacco-specific nitrosamines N-
nitrosonornicotine and 4-(methylnitrosamino)-
1-(3-pyridyl -l-butanone have been detected in
smokeless tobacco at levels 100 times higher
than the regulated levels of other nitrosamines
found in bacon, beer, and other foods
• . Animals exposed to these tobacco-specific
nitrosamines, at levels approximating those
thought to be accumulated during a human
lifetime by daily smokeless tobacco users,
have developed an excess of a variety of
tumors b’coz they nitrosamines can be
metabolized by target tissues to compounds
that can modify cellular genetic material.
• Some bioassays suggest that snuff may cause
oral tumors when tested in animals that are
infected with herpes simplex virus.
•  The factor common to all cancers is
considered to be a DNA mutation, either in
the germ line or, much more frequently, in
somatic cells.
• For cells to undergo a malignant neoplastic
transformation they need to be subjected to
two mutations, this is in accordance to the
double hit (impact) theory.
• Either one of the two mutations can be:
• genetic predisposition (oncogenes),
• viruses and
• environmental factors among which the polyaromatic
hydrocarbon subfractions contained in tar from
tobacco usage, and nitrosamines like, the tobacco-
specific N-nitrosamine (TSNA),
• N'-nitrosonornicotine (NNN), and
4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
• P53 is a "tumor suppressor gene" located on
the short arm of chromosome 17 (17p13.1).
P53 has a basic function in the cellular cycle
control and subsequently in the induction of
neoplastic processes. The protein p53, coded by
the gene with the same name, regulates
apoptosis.
• Apoptosis is an irreversible process that
conduces to natural cell death.
• Mutations in p53 eventuate in cessation of
apoptosis which allow for the growth and
development of abnormal cells. This over expression
of the mutated p53, in the oral cavity, seems to be
directly related to tobacco, alcohol and arica nut
(betel nut) usage.
• P16 is another tumor suppressor gene located on
the short arm of chromosome 9 (9p21-23). Genetic
mutations at the level of p16 have been reported in
a subset of chewing tobacco-induced oral cancers.
• The three components of cigarette smoke that
seem to interfere with wound healing are
nicotine,
• carbon monoxide
• hydrogen cyanide.
• Nicotine is absorbed in the lungs where it enters
the blood circulation and is capable of producing
specific effects such as diminished proliferation of
erythrocytes, fibroblasts and macrophages.
•  Nicotine induces platelet aggregation with
increased blood viscosity, this phenomenon
favors the formation of microclots leading to
capillary embolism and ischemia of the
affected tissues. Vasoconstriction is another
by-product of nicotine due to the release of
catecholamines. Catecholamines induce the
formation of chalones which interfere with
normal wound healing and epithelialization.
• Carbon monoxide has a greater capability for
binding to hemoglobin than that of oxygen,
thus reducing the amount of oxygen binding
to hemoglobin and diminishing the
distribution of oxygen to tissues with
consequent cellular hypoxia and interference
with normal wound healing.
• Hydrogen cyanide also participates in the
alteration of oxygen metabolism and
distribution, further delaying wound healing
and epithelialization.