JOHN R. SAMPEY Furman University, Greenville, South Carolina
IT
i~ a sad commentary on the emotional and intellectual immaturity of America that it took the present dorm on the relation of smoking t o lung cancer to awaken the population to the dangers of carcinogens. Scores of emotion-packed articles on the theme, "canrer by the carton" have appeared in popular magazines throughout the country. And on the other side, through the daily press, radio, and television, the multimillion-dollar advertising interests of the tobacco companies have rushed to the defense of the industry. One wonders how much understanding the general public has of how the final issue will he reached. The final decision will be made with little attention to the hue and cry now being raised. It will come after a long campaign in many srientific laboratories, and the results will be announced in the technical language of the medical literature. Already some 45 of these qtudies may be found in the current medical journals.
Chemical Carcinogens in Current Medical Literature
Chmieal
No. of articles
Amino acids .4minaszotoloene .%so dves
6 6 11
Renzidinc Benzpyrene I3wvllium eomwunds C;u:bon tetrachloride
38 6 6
7
&ton ail Dibmzanthracene Dibenzcarbazole ni~t,hvlstilhestrol
22 25 5
benzine Dimethylbenzanthraeene FMradiol
51
27
39
Chemical Fats Radioiodine 3'-Methvl-dimethvlamino"azobenrene Methylcholanthrene Nttphthylamine, beta. Nitroeen m u s t a r b ~etroieum Pituitary hormones Progesterone Silicates Stilbrstrol Tannic acid Tars Testosterone Thiouracil Tobacco Trypan blue Urethan Vitamins
No. of articles 9 21 17 112 15 12 20 10 5 5 i 8 6 8 11 45
7 25
7
16
Carcinogenesis became an experimental science 40 years ago when Yamagiwa and Ichikawa induced the first cancer by prolonged application of a coal-tar dist,illate to the ear skin of rabbits. For many decades t,he high incidence of skin cancer among the chimney sweeps of England had been considered an occupational disease. The discovery made by the two Japanese scientists opened the way for an experimental approach tu the hazards of carcinogens in industrial operations. The search today for carcinogenic agents has extended far beyond the bounds of industrial medicine. 4
The extent of the field maybe visualizedby summarizing some 850 articles of the last six years which describe experiments on t.he incidence of growth-promoting activity of numerous agents toward neoplasms (see the table).' Review articles and references to theoretical speculations and interpretations of mechanisms are not included in the 850 total. Hydrocarbons account for one-fourth of all current studies on carcinogens, methylcholanthrene alone being the agent in more than 100 articles. Benzanthwcene, benzpyrene, dibenzanthracene, dimethylbenzanthracene, and petroleum are other hydrocarbons inducing a variety of neoplastic growths in animals. AZOdyes and azo coloring materials used in foods have been tested extensively in the study of cancer of the liver. Dimethylaminoazobenzene (butter yellow), 3'-methyl-dimethylaminoazobenzene,aminoazotoluene, and other azo dyes have been employed to indure hepatomas in experimental animals. The teacher of organic chemistry will note the relatively simple strurture of other molecules in this list, of powerful carcinogens: 2-acetylaminofluorine, amino acids, carbon tetrachloride, fats, beta-naphthylamine. nitrogen mustards, tannic acid, thiouracil, and nrethan. Inorganic chemicals are much more useful as anticancer agent^,^ but the cancer-inducing properties of beryllium compounds, chromates, radioactive iodine, and silicates have been investigated extensively. The role of hormones in carcinogenesis is one of the most controversial subjects in the chemotherapy of cancer. Leading in the volume of current research are the sex hormones diethylstilhestrol, estradiol, progesterone, stilbestrol, and testosterone, the pituitary hormones, and cortisone. One of the most intriguing problems of cancer arises from the strange dual role played by many chemical molecules whirh act as both carcinogenic and anticancer agents. A recent summary of the current medical literature shows that one-third of the most frequently employed anticancer agents are found among the present list of most used cancer-inducing chemicals. The chemicals appearing in both lists are: cortisone, nitrogen mustards, hydrocarbons, estrogens, amino acids, urethan, vitamins, pituitary hormones, and testosterone. If we include biological agents, then three more groups appear on both lists, namely: viruses, with 41 studies on their anticancer activity and 13 re' SAMPEY,J. R., Am. J. Phun., 127, 53+4 (1955); J . So. Car. Med. Assoe., In press. J. R., Znd. Med. and St~rg.,22,30&1 (1953). SAMPEY, Studies,2 (No. 3), 12-18 (1955).
SEPTEMBER, 1955
449
ports on their carcinogenicity; tumor extracts, which million dollars annually on its cancer control program. have called forth 18 studies on inhibiting cancer and I n view of the little known about carcinogenic and an55 on inducing neoplasms; and extracts of normal tis- ticancer agents and the daily death rate of 600 victims sues, which have rated 12 articles on anticancer studies of this killer, we have much to do and much to learn. and 18 on car~inogenicity.~ It is even conceivable that the present hysteria over Currently the nation is spending some twenty- cigarettes and cancer may result in more funds for basic research on the chemotherapy of neoplastic diseases. a SAMPEY, J. R.,Seimce, In press.
