RESEARCH
New enzyme found in leukemia patients Fatal disease may be caused by altered DNA produced by polymerase that uses RNA from RNA-containing viruses
Dr. Robert C. Gallo and his coworkers find that a derivative of the drug rifampicin inhibits the DNA polymerase
An enzyme that may be a major link in the chain of events leading to human leukemia has been found in the blood of three leukemia patients. The discovery is particularly important if this fatal disease is caused—in at least some of its forms—by a virus. In the past five months, Dr. Robert C. Gallo of National Cancer Institute and Dr. Stringner ("Sue") S. Yang and Dr. Robert C. Ting of Bionetics Research Laboratories, Bethesda, Md., have jointly studied the lymphocytes in the peripheral blood of three patients with acute lymphocytic leukemia. They found that, in all three patients, these cells contained an RNAdependent DNA polymerase. On the other hand, they found no detectable amounts of this enzyme in lymphocytes of 48 normal people. Recognizing, of course, that additional data are needed, Dr. Gallo and his group are planning to look for this enzyme in other patients with leukemia or other forms of cancer believed to be caused by RNA viruses. Dr. Gallo and his associates are the first scientists to report the presence of RNA-dependent DNA polymerase in the cells of cancer patients—in fact, in the cells of any humans. In recent
months, several U.S. scientists have reported such an enzyme in RNA viruses and in cancerous tissue-culture cells of mice. Discovery of this enzyme in humans, which in the past few weeks has touched off intense excitement in the cancer research field, was disclosed by Dr. Gallo early last month at a closed meeting of the Pasteur Institute in Paris, France. Dr. Gallo and coworkers made their first published report of their findings in the Dec. 5 issue of Nature [228, 927 (1970)]. The enzyme they found is a type of DNA polymerase. That is, it is an enzyme involved in forming the DNA polymer, the basic hereditary material of the cell. DNA polymerase was first isolated back in 1956 by Dr. Arthur Kornberg, then at Washington University in St. Louis. Normally, a cell makes DNA by using another DNA molecule as the template for assembling the molecule's building blocks, the purine and pyrimidine nucleotides. Since DNA itself is the template for DNA synthesis, the enzyme required to do this is a DNAdependent DNA polymerase. The enzyme that Dr. Gallo and associates found in humans serves a different purpose. It forms DNA by using RNA as its template. The idea that DNA can be made from an RNA template was until recently considered by many scientists to be impossible. In fact, the term "DNA-dependent" DNA polymerase was never even used. Since scientists believed that DNA could be formed only off a DNA template, the term would have been regarded as absurdly redundant, like speaking of a canine dog. However, now that either a DNA or an RNA template can be used in synthesizing DNA, the terminology has had to be refined. Leukemia mechanism. As Dr. Gallo and associates visualize the process of lymphocytic leukemia, on the basis of the suggestive evidence presently available, the disease may begin when an RNA virus enters a normal lymphocyte precursor cell (a socalled "stem cell"). The virus carries with it the RNA-dependent DNA polymerase. Because of the presence of this enzyme the RNA virus can act as a template for the formation of
DUPONT mm AMOTION SOLVENT NEWS iiilllilililiiSiliSilKlliillll^iilllllliilil
•III
DMF used in enamine reactions further illustrates its versatility and efficiency in organic syntheses.
DMF is being used in a wide range of products involving many classes of organic syntheses. Recent examples include the following enamine reactions: Vilsmeier formylation a-Formyl compounds can be prepared from enamines by use of DMF instead of the usual formylation of ketones. a-Formylcyclohexanone can be prepared by the Vilsmeier formylation [Angew. Chem., Int. Ed. Engl., 4, 358 (1965)]
o
r
CO CI* CHjCU
CH3
?. /
0 + H •C - N
reflux
\ CH3
/•v
52% Yield
Tetrahydropyridines prepared from enamines A general route for the preparation of tetrahydropyridines is based on the reaction of 3-bromopropylamine hydrobromide with enamines in DMF. Octahydroquinoline can be prepared in one step by reacting 1-(1cyclohexene-1-yl) piperidine with 3-bromopropylamine hydrobromide in DMF [J. Org. Chem. 28, 3468 (1963)]
0-»(D
+ B r - C H 2 - C H 2 - C H 2 - N H 2 • HBr
DMF IOO-IIO°C Exothermic I hour
Discover the opportunities for improving products and processes with Du Pont DMF at 220 per lb. Economy in production-scale use DMF (dimethylformamide) is the least expensive ot the "super" (highly dipolar aprotic) solvents. In addition, easy recovery, high conversions and faster reaction rates result in low use-costs. Versatility and efficiency in chemical processes DMF is used in the manufacture of a wide range of products, involving many classes of organic reactions, often with existing equipment. Higher conversions and faster reaction rates are often possible with DMF, resulting in higher product yields. Product purity results from reduced by-product contamination. Easy recovery DMF can easily be recovered by simple distillation at atmospheric or reduced pressure. High recoveries (up to 99%) not only reduce production costs, but also improve pollution control. Du Pont's new DMF Recovery and Purification Bulletin provides basic data on methods and equipment for recovery of DMF in production operations. Mail the coupon for more information on Du Pont DMF.
Du Pont Company Room 7945 A Wilmington, Delaware 19898 Please send • DMF Bulletin • DMF Recovery and Purification Bulletin
N 8 0 - 8 4 % Yield
Enamine alkylation using DMF Enamines can be alkylated with electrophylic olefins by refluxing the materials in DMF [J. Am. Chem. Soc. 85, 207 (1963)]
Name. Title _ Company _ Street _State_
City \
>/ " N
+
CH3
°H
=
CHC00CH
2CHS
o \
DMF reflux
Zip
.Telephone.
CH3
3c=iirrji—ni—iczzjcmc
-C-CH2C00CH2CH5
DMF
" 56% Yield
R
E G . U S.PAT OFF-
Solids Removal Problem? Call on Hercules. (Our Environmental Services Division has ^ f ^ m ^ N l ) ^ . pwnfcipal. plant personnel, the people and polymers to help you— the;
