Effects of Tobacco Smoke on Animals and Man

Introduction

This report is timely because of the rapidly increasing incidence of degenerative disease afflicting mankind since the turn of the century. In 1962, over 500,000 people in the United States died of arteriosclerotic heart disease, 41,000 died of lung cancer, and 15,000 died of bronchitis and emphysema. In 1930, there were only 3,000 reported deaths from lung cancer, showing an extraordinary rise not equalled by cancer of any other site.

Deaths from arteriosclerotic, coronary and degenerative heart disease more than doubled from 1940 to 1962.

Reported deaths from chronic bronchitis and emphysema rose from 2,300 in 1945 to 15,000 in 1962. It is of considerable interest that the consumption of cigarettes increased from 49 per person, aged 15 years or over in the United States in the year 1900, to 3,958 in 1962. These figures, together with retrospective and prospective studies of human beings, plus animal experiments and pathological examination of post mortem specimens, leave little doubt that there is a definite association between the increased mortality in these areas and a marked increase in cigarette smoking. This is particularly true of carcinoma of the larynx and lung. Smoking is definitely related to chronic bronchitis and emphysema. Whereas male smokers have a higher incidence of coronary thrombosis than nonsmokers, the causative relationship here is not as convincing: nevertheless, it is probably operative.

Much of this material is taken from “Smoking and Health, Report of the Advisory Committee to the Surgeon General of the Public Health Service”, and I am indebted to this committee for their excellent research.

Ingredients

1. The tobacco leaf contains many substances which are found in other plants and which include cellulose, proteins, starches, sugars, alkaloids, plastic substances, hydrocarbons, phenols, fatty acids, isoprenoids, sterols, and inorganic minerals. Some 500 compounds may be included. Two of these groups are specific for tobacco; namely, nicotine and nornicotine, myosmine and anabasine. The formulae appear below:

The second group of compounds are described as isoprenoids, since they are divisible into units of isoprene, the building principle of rubber, of the red pigment of the tomato, and of the yellow pigment of the carrot, as illustrated below.

In other words, the isoprenes are the basic unit of terpenes and one of the squalenes has been found in tobacco smoke.

Tobacco smoke is a heterogeneous mixture of gases, uncondensed vapors, and liquid particulate matter. It is a concentrated aerosol with billions of particles per c.c., the medium sized being about 0.5 micron in diameter. The gaseous phase is the most important and will be discussed later.

2. Tar amounts to 3-40 milligrams per cigarette. The temperature during a puff averages 884 degrees Centigrade and without air, 835 C. Pyrolytic reactions include oxidation, dehydrogenation, cracking, re-arrangement, and condensation.

3. The main ingredients of the smoke, in addition to tar, are acids, glycerol, glycol, alcohols, aldehydes, and ketones, aliphatic and aromatic hydrocarbons, phenols, and the terpenes and terpenoids mentioned above. Squalene, incidentally, can be cyclicized and may react with air to form hydroperoxides, which have carcinogenic properties. Ethylene glycol and glycerol may be additives. Trace amounts of TDE and endrin have been detected in commercial cigarettes and cigarette smoke. Guthion and Sevin residues have also been found in the mainstream of cigarette smoke. Phenols and hydroperoxides may act as co-carcinogens.

Non-carcinogenic, aromatic hydrocarbons included benzene, toluene, and other alkyl benzenes, such as fluorene, anthracene, and phenanthrene. In this type of compound, 4-6 condensed rings usually indicate carcinogenicity. Twenty-seven of these compounds were found to be negative from this standpoint.

However, dibenzo (aH) anthracene and benzo (a) pyrene are present and are carcinogenic for animals when concentrated. Dibenzo (ai) pyrene is a potent carcinogen (0.5 mg. injected into an inbred strain of mice induced sarcomas in 98% in 24 weeks). Since only about 16 mcg. per one thousand cigarettes has been found, there is no evidence that this is important clinically. Tar from cigarettes when painted on the skin of mice has 40 times the activity of the most active constituent, namely, dibenzo (a) pyrene. This indicates that the whole is greater than the most important part and fits in with what we suspect clinically as a summation effect of minute amounts of many chemicals in air, food, and water. Phenol, as mentioned before, may be a co-carcinogen, as may fatty acids. Parenthetically, 70 to 80% of the latter are removed by cellulose acetate filters.

The gas phase of cigarette smoke is approximately 60%. This is made up of about 73% nitrogen, 10% oxygen, 9.5% carbon dioxide, 4.2% carbon monoxide, 1% hydrogen sulfide, and 0.6% methane. Other gases found in smaller quantities include acetylene, ethylene, propylene, acetaldehyde, acrolein, methanol, acetone, Nh3, H2S, and HCN. Small amounts of 40 other chemicals have been identified and most of them are irritants. In this respect, Hilding showed that cigarette smoke is capable of seriously inhibiting the transport activity of ciliated cells such as are found in the respiratory tract. The smoke from a regular cigarette was found to produce 50% reduction in activity after exposure to two or three puffs. The gaseous phase was the one found to be active. Assays of known components of the gas phase showed that HCN, formaldehyde, acetaldehyde, acrolein, and ammonia possess ciliary paralyzing activity. Interestingly enough, none of these is present in the gaseous phase at levels high enough to produce the effect noted for tobacco smoke. Therefore an additive effect is involved. Whereas arsenic composes about 6.2 parts per million of the smoke, it seems to be no hazard since city air contains ten to 40 times as much.

In addition to the substances mentioned above, sugars, humectants, synthetic flavors, licorice, menthol, vanillin, and rum are often added. Natural coumarins are present and in the past, artificial coumarin has been added. Glycerin is an important source of acrolein if present.

Physiological Effects

1. Nicotine. The nicotine content of the smoke inhaled from one cigarette varies between one and two milligrams and the intake, of course, depends upon the number smoked. It has been estimated that 30 to 80 milligrams per day of nicotine is ingested by those using cigars, chewing tobacco and snuff. (Inhaling the smoke from 30 cigarettes would be equivalent)

The primary effects of nicotine include tachycardia, rise in blood pressure, discharge of epinephrine from the adrenal medulla, release of anti-diuretic hormone from the posterior pituitary, and a direct action on sympathetic and parasympathetic ganglia. This comprises stimulation followed by depression. Ganglia are rendered more susceptible to acetylcholine. The reactions are complicated and unpredictable. In animals, after neopontine resection, blood levels of 10 to 20 mcg. per kilogram give an arousal pattern. There is no direct evidence of disease produced by nicotine except Buerger’s disease; nor is there any unusual mortality from the use of nicotine per se. It does, however, produce vascular spasm and lowered skin temperatures. A drop of seven degrees Fahrenheit is common for the fingers of smokers who inhale.

2. Other constituents of tobacco smoke. Tobacco smoke causes irritation of the mouth, tongue, and nose. It also affects the trachea, bronchi and alveoli, as well, when smoke is inhaled. Leukoplakia of the mouth is not uncommon; the bronchial epithelium frequently shows hypertrophy of the basal layer, loss of cilia, metaplasia, increase in goblet cells, atypical basal cells, fibrosis of blood vessels and probable damage to alveoli. Interestingly enough, the trachea does not often show these changes and it should be remembered that carcinoma of the trachea is uncommon. 

In addition to inducing cancer of the buccal cavity, the lung, bronchial tubes, esophagus and larynx tobacco seems to increase the tendency towards bladder cancer. Interestingly enough, large doses of Vitamin C or ascorbic acid may control recurrence of this tumor probably as a result of redox action.

Clinical Symptoms and Signs

In susceptible individuals, smoking cigarettes may produce any of the following symptoms: tachycardia, marked fatigue, extra systoles, nasal congestion, post-nasal drip, sore tongue, pharyngitis, laryngitis, tracheitis, and bronchitis with chronic cough, which may be dry or productive. Morning nausea is not uncommon and is aggravated by alcoholism.

There may also be neuritic pains, spasms of the trapezius muscles with aching, partial loss of taste and smell, bad taste, and dryness of mouth and nose, constipation or diarrhea, and temporarily increased colonic activity. Since the latter is often followed by depression, smokers who frequently depend upon the first cigarette to produce a bowel movement, are, in fact, constipated. If they give up tobacco, they may find that bowel movements are more frequent and occur naturally after meals.

1. Symptoms result both from the irritative effects of tobacco smoke and from the action of nicotine on autonomic ganglia. In sensitive individuals, the latter effect is sustained stimulation of the sympathetic part of the autonomic nervous system. Thus, many smokers are prepared for flight or fight and the long term result tends to be physiologically catabolic rather than anabolic. There may thus be a significant effect over the years on nutrition and homeostasis.
2. Clinical signs and symptoms include tachycardia in 80% of those studied by me over the years. Elevated blood pressure occurs in some smokers and redness of the pharynx and larynx is universal. So is chronic cough, lowered resistance to infection and a low grade bronchitis with a tendency towards emphysema. There is decreased lung ventilation.
3. The mortality of cigarette smokers versus non-smokers, as might be expected, is definitely related to the number of cigarettes smoked and the length of time over which the smoker has consumed tobacco. Other factors of importance will be mentioned later.

Contributing factors:

1. Air pollution.There is definite augmentation of the mortality rate of carcinoma of the lung in the larger cities of England, which suggests that air pollution may play a part. This, however, is not obvious in the United States.
2. Inheritance. Studies in this area are inconclusive.
3. Nutrition. To date, this has received little attention.

Smoking Tests

About 20 years ago, working along the lines of the late Arthur F. Coca, I studied some 400 patients from the standpoint of tobacco sensitivity. A simple smoking test done in the office revealed 80% of the cases to be hypersensitive to tobacco smoke. Patients were advised not to smoke after 12:00 p.m. and to come into the office without having smoked the first morning cigarette. After resting five minutes, a basal blood pressure and pulse rate were taken. A cigarette was then smoked and the blood pressure and pulse repeated after five minutes. A rise in pulse rate of eight beats or more per minute was considered significant and was usually accompanied by a definite rise in blood pressure, including both the systolic and diastolic pressures. Some individuals would develop an increase in pulse rate of 30 to 40 beats per minute with a commensurate rise in blood pressure. The 20% who failed to react were then asked to smoke a second cigarette and the readings repeated. If there was no change, it was assumed that these people had a nervous system which was relatively non-reactive to nicotine. In a number of instances, the graphic rise in pulse rate and blood pressure was enough to convince smokers that they were whipping a tired horse and this helped them to quit the habit.

Discussion

1. From the practical standpoint, it is inconsequential as to whether the reaction described above to smoking tobacco is truly allergic or a hypersensitive reaction. At any rate it is important. Thus, tobacco smoke may be described or classed as a major allergen and for the purposes of identifying food and chemical allergens, tobacco smoking masks the reactions of food allergy on the pulse rate. Although smoking irritates asthmatics, it is seldom the primary cause of bronchial asthma. Many smokers become much more susceptible to contact with tobacco smoke once they have stopped smoking themselves.
2. One of the factors concerned with habituation may be sympathetic stimulation. As Theron G. Randolph, M.D., has so beautifully described in the past, smokers who are addicted to tobacco, feel better from repeated stimulation during the adaptive phase.
3. It is obvious that the harmful effects of cigarette smoking outweigh any possible benefits. Nevertheless, psychological and social factors, plus habituation, make it difficult for most confirmed smokers to give up the habit. Education and social pressures are most logical and the Department of HEW has started a massive propaganda campaign along these lines. (The ban on smoking in this room is a good example of acceptable pressures to help protect the public, as well as to suggest that smoking is both harmful and objectionable.)
4. To date there has been little effort to explain individual differences in response to tobacco smoke and other noxious environmental contacts. I will but mention a few of these other factors:
   1. It seems logical that a good inheritance with normal active enzyme systems should increase resistance to the detrimental effects of tobacco smoke and nicotine.
   2. The physical degeneration which is afflicting practically everyone in civilized countries as a result of refined and processed foods over several generations must be an important factor. Highly nutritious food raised on fertile soil and consumed in as near a natural state as possible should be high in protein, unrefined carbohydrates, minerals, vitamins, and essential fats for optimum physiological function. Our devitalized and chemicalized foods today do not provide the necessary nutrients in adequate quantities.It has been estimated that smoking one cigarette uses up about 25 mg. of ascorbic acid. This may or may not be correct. We do know that Vitamin C has important detoxicating functions in addition to its other physiological actions. Therefore, smokers, and probably others, would be wise to ingest about 2,000 milligrams of ascorbic acid daily.
   3. Gilbert Delldorf, about 35 years ago, performed an experiment pointing out the importance of Vitamin A as a protective factor for the bronchial and tracheal epithelium. He inserted a plain cotton thread in the trachea of rabbits. This acted as a foreign body. In rabbits deficient in Vitamin A, the tracheal columnar ciliated epithelium changed to a stratified squamous type. This was not true in the animals who received adequate Vitamin A. The conclusions are obvious. A study of the effects of tobacco smoke on animals and human beings indicates that tobacco smoking simply introduces one more severe stress in man’s environment. I am again reminded that the only sound approach to health and the prevention and control of disease must be based primarily on ecology, nutrition, and biochemistry.

 

References Cited:

1. “Smoking and Health, Report of the Advisory Committee to the Surgeon General of the U.S. Public Health Service,” U.S. Department of HEW (Public Health Service Publication No. 1103, obtainable from the Supt. of Documents, U. S. Government Printing Office, Washington, D.C. 20402–price, $1.25.)
2. The Project for Research on Tobacco and Health, 1964-8, American Medical Association Education and Research Foundation, Chicago.
3. Report of the Scientific Director, Clarence Cook Little, S.C.D., 1969-70. A.M.A. E.R.F., Chicago.