Chemistry Has New Role in Cancer Research A STAFF REPORT T HE part which chemistry can supply in cancer research was discussed by five workers in this field from Memorial Hospital, N e w York, before the February meeting of the North Jersey Section, AMERICAN CHEMICAL SOCIETY, held at t h e P u b -
lic Service Auditorium, Newark, X . .J. The speakers were Cornelius P. Rhoads, who addressed the meeting o n "The Metabolism of the Carcinogenic* Hydrocarbons*'; Charles J. Kensler, o n "The Mechanism of Cancer Production by D i methylaminoazobenzene and Allied Compounds**; Joseph Burchenal, "The Nitrogen Mustards in Cancer Therapy**; and Konaird Dobriner and David Fukushima on "Steroid Hormone Metabolism and Cancer Research". None of the speakers read from a prepared paper, and the discussions were based almost entirely on graphic presentations of laboratory and clinical results with slides. Dr. Rhoads, who opened and closed the talks, said the researches at Memorial Hospital g o t under way some eight years a g o in connection with the study of leukemia, a form of blood cancer. Dibenzanthracene, a carcinogenic or cancer-inducing compound, was fed t o rabbits and in metabolism studies it was found that a dihydroxy derivative was excreted. Adsorption curves were shown for dibenzanthraceno, and there was evidence that this carcinogen is converted b y the mammal into a noncarcinogenic substance. In outlining probable future cancer research, D r . Rhoads said t h a t a number of abnormal steroids are found in the urine of cancer patients. A vast number of chemical compounds are required for the purpose of these studies and for testing the effects of anticarcinogenic substances. An empirical search is under way for chemot hcrapeutic compounds which m a y be used in cancer. Many of these are in the hands of chemists, and t h e work will call for greater efforts in many branches of chemistry. Dr. Kensler reviewed a number of important phases of liver cancer produced b y azo carcinogen and efforts t o work out protective factors i n liver and milk. Rats which had been fed yellow azo compounds had also been administered various dietary supplements for metabolism studies. T h e incidence of tumor was found t o be one twentieth to one tenth when the test animals were fed o n rice, carrots, and milk and after administration of the carcinogen had been stopped for 60 days. Riboflavin (B_») and casein were also used in the diet supplements. Chemically, azo carcinogen is known as p-dimethylaminobenzene - 1 - azonaphthal.cne, or as A",.Y'-dimethyl-/>-aminoazo-
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benzene. T h e metabolism of this compound in the rat was described, as was t h e inhibition of cellular enzymes of the S H type of known and postulated intermediary metabolites. Enzymatic activities of liver cells in vitro were inhibited when t h e cells were incubated with D M B . Treatments
Tested
chloride salts which are stable, watersoluble, and easy t o handle. Methyl-bis(/3-chloroethyl)amine was said to be extremelj' reactive with water or organic groups. At critical concentrations, it apparently interferes selectively with cell division, especially in cells undergoing frequent division. In this respect, it is similar to the effects obtained with xrays. T h e methyl-bis compound is i n jurious to normal and neoplastic tissues and in s o m e instances is more damaging to t h e latter. I t can b e shown therefore to prolong the life of animals bearing certain types of tumors. N e w compounds meanwhile are being examined systematically b y laboratory methods in an effort t o obtain a more selective action o n cancer cells. T h e speakers were introduced b y W. O. Baker, Bell Telephone Laboratories, Murray Hill, X . J., i n the absence of William J. Sparks, Standard Oil Development Co., Elizabeth, X. J., chairman of the North Jersey Section. T h e meeting was preceded by an i n formal dinner held a t the Newark Athletic Club. T h e section is anxious to assist, in t h e biochemical and other phases of cancer research, said Dr. Baker in calling attention to the large number of industrial and pharmaceutical laboratories in northern N e w Jersey. Many of them are equipped for spectrographs, x-ray, and electron diffraction work.
D r . Burchenal's discussion was devoted for the most part t o the use of the recently developed nitrogen mustard compounds in cancer treatment. These products, closely related chemically to the mustard gas of chemical warfare, do not offer very much a t this time although t h e y have proved effective in treating some forms of cancer such as leukemia and Hodgkins disease, a malady of the lymph glands i n volving progressive anemia. They appear to interfere with the division of certain types of cells which characterize cancer growth. Other cancer types which respond to t h e nitrogen mustards are carcinoma of t h e lung, m3rcosis fungoides, lymphosarcoma, and polycythemia. While extensive or advanced cancer in man has n o t been cured through this therapy, use of t h e compounds in connection with x-rays have in some cases halted the spread of the d i s ease and alleviated pain. T h e x-ray alone does about everything accomplished t h u s far b y the nitrogen mustards, t h e speaker said, and evidently does i t better. David Karnofsky Memorial Hospital, was a co-worker with Dr. Burchenal in this study. A number of modifications of the nitrogen mustards are possible, and chemists were asked to consider t h e likelihood of substitutions of the nitrogen in the formula. Many variations were IV. O. Baker; C. J . Kensler urtd Joseph Above. held possible. Konaird Dobriner, C /*. Rhoads, and Davifl Beloiv. Nitrogen mus-
Burchenal. Fukushima
tards, one type substance of which is bis(/3chloroethyl) ami n e hydrochloride, are nitrogenous analogs of sulfur mustard, bis(/Sehloroethyl) sulfide. The nitrogen mustards can form hydro-
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