'Why' and 'how' tobacco is harmful??

Tobacco contains the alkaloid nicotine, a powerful neurotoxin that is particularly harmful to insects. All means of consuming tobacco result in the absorption of nicotine in varying amounts into the user's bloodstream, and over time the development of tolerance and dependence.

Absorption quantity, frequency and speed seem to have a direct relationship with how strong a dependence and tolerance, if any, might be created. A lethal dose of nicotine is contained in as little as one half of a cigar or three cigarettes; however, only a fraction of the nicotine contained in these products is actually released into the smoke, and most clinically significant cases of nicotine poisoning are the result of concentrated forms of the compound used as insecticides. Other active alkaloids in tobacco include harmala.

Major hazards of tobacco use, however, involve carcinogenic compounds in tobacco and tobacco smoke.

The United States's Centers for Disease Control and Prevention describes tobacco use as "the single most important preventable risk to human health in developed countries and an important cause of premature death worldwide".

An indirect public health problem posed by cigarettes is that of accidental fires, usually linked with consumption of alcohol. Numerous cigarette designs have been proposed, some by tobacco companies themselves, which would extinguish a cigarette left unattended for more than a minute or two, thereby reducing the risk of fire. However the tobacco companies have historically resisted this idea, on the grounds that the nuisance involved in having to relight a cigarette left untouched for too long would reduce their sales. In fact, untreated tobacco formed into a cigarette will extinguish itself relatively quickly if left alone, and as a result cigarette tobacco is treated chemically to allow it to smolder indefinitely.

The main health risks in tobacco smoking pertain to diseases of the cardiovascular system, in particular smoking being a major risk factor for a myocardial infarction (heart attack), diseases of the respiratory tract such as Chronic Obstructive Pulmonary Disease (COPD) and emphysema, and cancer, particularly lung cancer and cancers of the larynx and tongue. Prior to World War I, lung cancer was considered to be a rare disease, which most physicians would never see during their career. With the postwar rise in popularity of cigarette smoking, however, came a virtual epidemic of lung cancer.

A person's increased risk of contracting disease is directly proportional to the length of time that a person continues to smoke as well as the amount smoked. However, if someone stops smoking, then these chances steadily although gradually decrease as the damage to their body is repaired.
Diseases linked to smoking tobacco cigarettes include:
• lung cancer and other cancers
• stroke
• peripheral vascular disease
• birth defects of pregnant smokers' offspring
• Buerger's disease (thromboangiitis obliterans)
• impotence
• chronic obstructive pulmonary disease, emphysema and chronic bronchitis in particular

Cigar and pipe smokers tend to inhale less smoke than cigarette smokers, so their risk of lung cancer is lower but is still several times higher than the risk for nonsmokers. Pipe and cigar smokers are also at risk for cancers of the oral cavity, larynx (voice box), or esophagus, a risk which was widely hypothesized before any link between smoking and cancer was scientifically proved as seen in the news coverage of the tobacco-related cancers of two American presidents; Ulysses S. Grant died in 1885 at age 63 after a long and painful public battle with throat cancer which was widely assumed at the time to be the result of his lifelong cigar habit, and his successor Grover Cleveland was diagnosed in 1893 with cancer of the left jaw, which was frequently remarked upon by the press and public as the side where he usually had a cigar clamped. Similarly, cancer of the mouth and jaw is also a risk for chewing tobacco.

It is generally assumed that the major motivational factor behind smoking is the nicotine it contains. However, the practice of ingesting the smoke from a smoldering leaf generates an enormous number of active chemical compounds, loosely lumped together as 'tar', many of which are biologically reactive and potential health dangers. (Chewing tobacco is also carcinogenic, likely because similar compounds are generated in the practice of curing it; the Nordic snus, which is steam cured and therefore does not generate these compounds, is much less carcinogenic.) There are around 3000 chemicals found in tobacco smoke.

Below are chemicals of known or suspected carcinogenicity:
• Carcinogenic:
o 4-Aminobiphenyl
o Benzene
o Cadmium
o Chromium
o 2-Naphthylamine
o Polonium-210
o Radon
o Vinyl chloride
o Formaldehyde
• Probably carcinogenic to humans:
o Acrylonitrile
o Benzo[a]anthracene
o Benzo[α]pyrene
o 1,3-Butadiene
o Dibenz(a,h)anthracene
o N-Nitrosodiethylamine
o N-Nitrosodimethylamine
• Possibly carcinogenic to humans:
o Acetaldehyde
o Benzo[b]fluoranthene
o Benzo[j]fluoranthene
o Benzo[k]fluoranthene
o Dibenz[a,h]acridine
o Dibenz[a,j]acridine
o 7H-Dibenz[c,g]carbazole
o Dibenzo(a,i)pyrene
o Dibenzo(a,I)pyrene
o 1,1-Dimethylhydrazine
o Hydrazine
o Indeno[1,2,3-cd]pyrene
o Lead
o Lead 210
o 5-Methylchrysene
o 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
o 2-Nitropropane
o N-Nitrosodiethanolamine
o N-Nitrosomethylethylamine
o N-Nitrosomorpholine
o N'-Nitrosonornicotine (NNN)
o N-Nitrosopyrrolidine
o Quinoline
o iv ortho-Toluidine
o Urethane (Ethyl Carbamate)

Long term exposure to other compounds in the smoke, such as carbon monoxide, cyanide, and other compounds that damage lung and arterial tissue, are believed to be responsible for cardiovascular damage and for loss of elasticity in the alveoli, leading to emphysema and COPD.
Tobacco and spontaneous abortion

A number of studies have shown that tobacco use is a significant factor in spontaneous abortions among pregnant smokers, and that it contributes to a number of other threats to the health of the fetus. Second-hand smoke appears to present an equal danger to the fetus, as one study noted that “heavy paternal smoking increased the risk of early pregnancy loss.” Many governments require printed rotating health warnings on cigarette packages. Often, one of these notes the negative effects of smoking on a fetus.

Radioactive components of tobacco:
In addition to chemical, nonradioactive carcinogens, tobacco and tobacco smoke contain small amounts of lead-210 (210Pb) and polonium-210 (210Po) both of which are radioactive carcinogens. Lead 210 is a product of the decay of radium-226 and, in turn, its decay product, radon-222; lead 210 then decays to bismuth-210 and then to polonium 210, emitting beta particles in both steps. Tarry particles containing these elements lodge in the smokers' lungs where airflow is disturbed; the concentration found where bronchioles bifurcate is 100 times higher than that in the lungs overall. This gives smokers much more intense exposure than would otherwise be encountered. Polonium 210, for instance, emits high energy alpha particles which because of their large mass are considered to be incapable of penetrating the skin more than 40 micrometres deep, but do considerable damage (estimated at 100 times as much chromosome damage as a corresponding amount of other radiation) when a process such as smoking causes them to be emitted within the body, where all their energy is absorbed by surrounding tissue. (Polonium 210 also emits gamma rays).

The radioactive elements in tobacco are accumulated from the minerals in the soil, as with any plant, but are also captured on the sticky surface of the tobacco leaves in excess of what would be seen with plants not having this property. As might be expected, the radioactivity measured in tobacco varies widely depending on where and how it is grown. One study found that tobacco grown in India averaged only 0.09 pCi per gram of polonium 210, whereas tobacco grown in the United States averaged 0.516 pCi per gram. Another study of Indian tobacco, however, measured an average of 0.4 pCi of polonium 210 per cigarette, which also would be approximately a gram of tobacco. One factor in the difference between India and the United States may be the extensive use of apatite as fertilizer for tobacco in the United States, because it starves the plant for nitrogen, thereby producing more flavorful tobacco; apatite is known to contain radium, lead 210, and polonium 210. This would also account for increased concentration of these elements compared to other crops, which do not use this mineral as fertilizer.

Smoke from one cigarette is reported to contain 0.0263 - 0.036 pCi of polonium 210, which is equivalent to about 0.1 pCi per milligram of smoke; or about 0.81 pCi of lead 210 per gram of dry condensed smoke. The amount of polonium 210 inhaled from a pack of 20 cigarettes is therefore about 0.72 pCi. This seems to be independent of any form of filtering or 'low tar' cigarette. This concentration results in a highly significant increase in the body burden of these compounds. Compared to nonsmokers, heavy smokers have four times greater radioisotope density throughout their lungs. The polonium 210 content of blood in smokers averages 1.72 pCi per kilogram, compared to 0.76 pCi per kilogram in nonsmokers. Higher concentrations of polonium 210 are also found in the livers of smokers than nonsmokers. Polonium 210 is also known to be incorporated into bone tissue, where the continued irradiation of bone marrow may be a cause of leukemia, although this has not been proved as yet.

The alpha particle dosage from polonium 210 received by smokers of two packs a day has been measured at 82.5 millirads per day, which would total 752.5 rads per 25 years, 150 times higher than the approximately 5 rem received from natural background radiation over 25 years. Other estimates of the dosage absorbed over 25 years of heavy smoking range from 165 to 1,000 rem, all significantly higher than natural background. In the case of the less radioactive Indian tobacco referred to above, the dosage received from polonium 210 is about 24 millirads a day, totalling 219 rads over 25 years or still about 40 times the natural background radiation exposure. In fact, all these numbers of total body burden are misleadingly low, because the dosage rate in the immediate vicinity of the deposited polonium 210 in the lungs can be from 100 to 10,000 times greater than natural background radiation. Lung cancer is seen in laboratory animals exposed to approximately one fifth of this total dosage of polonium 210.

Whether the quantities of these elements are sufficient to cause cancer is still a matter of debate. Most studies of carcinogenicity of tobacco smoke involve painting tar condensed from smoke onto the skin of mice and monitoring for development of tumors of the skin, a relatively simple process. However, the specific properties of polonium 210 and lead 210 and the model for their action, as described above, do not permit such a simple assay and require more difficult studies, requiring dosage of the mice in a manner mimicing smoking behavior of humans and monitoring for lung cancer, more difficult to observe as it is internal to the mouse.

Some researchers suggest that the degree of carcinogenicity of these radioactive elements is sufficient to account for most, if not all, cases of lung cancer related to smoking. In support of this hypothetical link between radioactive elements in tobacco and cancer is the observation that bladder cancer incidence is also proportional to the amount of tobacco smoked, even though nonradioactive carcinogens have not been detected in the urine of even heavy smokers; however, urine of smokers contains about six times more polonium 210 than that of nonsmokers, suggesting strongly that the polonium 210 is the cause of the bladder carcinogenicity, and would be expected to act similarly in the lungs and other tissue. Furthermore, many of the lung cancers contracted by cigarette smokers are adenocarcinomas, which are characteristic of the type of damage produced by alpha particle radiation such as that of polonium 210. It has also been suggested that the radioactive and chemical carcinogens in tobacco smoke act synergistically to cause a higher incidence of cancer than each alone.
Skeptics of the role of polonium 210 in lung cancer note that it is soluble in water, and thus would be excreted (confirmed by the high polonium 210 concentrations in the urine of smokers, referred to above). However, the inhibition of the clearing action of the cilia in the respiratory tract by tobacco smoke, the stickiness of the particles of tar precipitated from the smoke, and deposits within the lung of insoluble lead 210 which then breaks down into polonium 210, have all been postulated as mechanisms by which polonium 210 exposure continues for long periods. Even after having stopped smoking for a year, concentrations of lead 210 and polonium 210 in rib bones and alveolar lung tissue remain twice as high in ex-smokers as in those who had never smoked.