Biographical Memoirs Volume 58 (1989) / Chapter Skim
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Charles Heidelberger
Charles Heidelberger
Pages 258-303
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From page 259... ...
He pioneered in the use of 3H- and i4C-labeled carcinogenic polycyclic hycirocarbons in the study of their metabolism and their interactions with target tissues. He was an early investigator of the development of systems for the malignant transformation by chemicals of mammalian cells in culture, and with his colleagues he clevelope(1 one of the most widely used systems for the transformation of mouse fibroblasts.
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From page 260... ...
Both Nina and Michael Heiclelberger had a talent for and interest in music, and they made their home a center for its enjoyment. At the time of Charlie's birth, Michael Heidelberger was already establishecl at the Rockefeller Institute for Meclical Research as a promising young organic chemist.
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From page 261... ...
he gave the summer lectures in organic chemistry while Fieser was on sabbatical leave. Although Fieser had set aside his research on the carcinogenic polycyclic aromatic hy(lrocarbons during the war years, the laboratory at Harvard introclucect Heidelberger to these carcinogens, which became central to his later research.
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From page 262... ...
clibenz~a,h~anthracene caught the attention of Harold P Rusch, director of the then relatively new McArdIe Laboratory for Cancer Research at the University of Wisconsin.
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From page 263... ...
Heidelberger's later studies of nucleic acid pyrimidines were built on this experience. CARCINOGENIC POLYCYCLIC AROMATIC HYDROCARBONS Heidelberger's synthesis of [l4C]
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From page 264... ...
But because of technical problems related to the determination of tritium in cesium chloride solutions in the Heidelberger laboratory, the first definitive report on the covalent binding of polycyclic aromatic hydrocarbons to DNA of target tissues was that of P
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From page 265... ...
In 1962 Heiclelberger took a sevenr~onth sabbatical to work with Lasnitzki at the Strangeways Laboratory in Cambridge, England, to learn the techniques required for the clevelopment of an organ culture system anti to develop a background in the cellular aspects of biology. On returning to the McArdle Laboratory, Heidelberger treated organ cultures of mouse prostate with polycyclic aromatic hydrocarbons, looking for neoplastic properties in the cultures.
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From page 266... ...
Heidelberger and his associates showed that there was a general quantitative relationship between the in viva carcinogenic activities of polycyclic aromatic hydrocarbons ant! their abilities to cause malignant transformation of these cultures!
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From page 267... ...
Starting in the early 1950s, he turned his interest in the biosynthesis of nucleic acids in normal and tumor tissues andfrom his graduate student days—in chemotherapy toward a search for pyrimiclines that would be therapeutic for cancer. Following a 1954 report by R
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From page 268... ...
In acIdition to 5-fluorouracil, Heiclelberger's interest in fluorinated pyrimidines lect to the syntheses in his laboratory of 5-fluorodeoxyuridine (which has received limited use in cancer chemotherapy) , 5-fluorocytosine (clinically effective against yeast and fungal infections)
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From page 269... ...
a Distinguished Professor of the University of Southern California in 1981. Although his untimely death cut short his work, Heidelberger livecl to see the University of Southern California Comprehensive Cancer Center become a major center for cancer research.
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From page 270... ...
, Papanicolaou Award of the Papanicolaou Institute for Cancer Research (1978) , Founcler's Award of the Chemical Industry Institute of Toxicology ~1982)
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From page 271... ...
These meetings, which usually lasted several hours on Monday evenings, included discussion of all of the research in progress in the lab. Organic chemists learned about biological problems, and biologists became familiar with discussions of synthetic organic chemistry.
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From page 272... ...
Music was a highlight of Heidelberger's life. He learned to play the violin as a young boy, was a member of the Harvard symphony orchestra in college, and continued to play chamber music throughout his life.
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From page 273... ...
During the intervening period, except for periods of intense therapy, he continued his work. As in the case of his mother's death from breast cancer in 1946, which he cited as one of his reasons for going into cancer research, Heidelberger's illness intensified his concern to find an adequate chemotherapy for cancer patients.
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From page 274... ...
Lepkovsky. Concerning the mechanism of the mammalian conversion of tryptophan into kynurenine, kynurenic acid and nicotinic acid.
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From page 275... ...
LePage. Incorporation of glycine-2-C~4 into proteins and nucleic acids of the rat.
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LePage. In vivo studies on incorporation of glycine-2-C~4 into proteins and nucleic acid purines.
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From page 277... ...
Intramolecular heterogeneity in nucleic acid biosynthesis.
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From page 278... ...
Grunberg. Fluorinated pyrimidines.
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From page 279... ...
Negative data from cancer chemotherapy screening. In: Cancer Research Supplement on Cancer Chemotherapy Screening Data, pp.
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Studies on nucleic acid biosynthesis in Ehrlich ascites cells suspended in a medium permitting growth.
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From page 281... ...
Some effects of 5-fluoroorotic acid and 5fluorouracil on the soluble ribonucleic acid of rat liver. Biochim.
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From page 282... ...
Experimental and clinical use of fluorinated pyrimidines in cancer chemotherapy. Cancer Res., 23: 1226-43.
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From page 283... ...
The design and application of pyrimidine antimetabolites for the control of nucleic acid metabolism. (In Russian.)
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From page 284... ...
Fluorinated pyrimidines: Biochemically and clinically useful antimetabolites. In: Nucleic Acids, Structure, Biosynthesis, and Function, pp.
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From page 285... ...
Iype. Malignant transformation in vitro with carcinogenic hydrocarbons.
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From page 286... ...
Chen. Quantitative studies on the malignant transformation of mouse prostate cells by carcinogenic hydrocarbons in vitro.
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From page 287... ...
XXXVII. Effects of 5-trifluoromethyl-2'-deoxyuridine on the synthesis of deoxyribonucleic acid of mammalian cells in culture.
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From page 288... ...
Antigenicity of cells derived from mouse prostate cells after malignant transformation in vitro by carcinogenic hydrocarbons. Cancer Res., 30: 1593-97.
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From page 289... ...
Metabolism of polycyclic aromatic hydrocarbons in cell cultures. Cancer Res., 31:2162-67.
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Transformation of hamster embryo cells by epoxides and other derivatives of polycyclic hydrocarbons. Cancer Res., 32: 1391-96.
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From page 291... ...
Establishment and characterization of a cloned line of C3H mouse embryo cells sensitive to postconfluence inhibition of division. Cancer Res., 33:3231-38.
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From page 292... ...
Cyclopentatf~isoquinoline derivatives designed to bind specifically to native deoxyribonucleic acid.
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From page 293... ...
Cell-cycle variations in oncogenic transformation in synchronized mouse embryo cells in culture. In: The Cell Cycle and Malignancy, pp.
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From page 294... ...
Rapp. Oncogenic transformation of C3H/lOTl/2 clone 8 mouse embryo cells by halogenated pyrimidine nucleosides.
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From page 295... ...
Liver homogenate-mediated mutagenesis in Chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins. Mutat.
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Cancer Res., 39:131-38. Oncogenic transformation of cell cultures by polycyclic aromatic
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From page 297... ...
Ultraviolet light in the oncogenic transformation of cultured C3H/lOTl/2 mouse embryo cells.
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From page 298... ...
Metabolism of benzofa~pyrene and oncogenic transformation in C3H/lOTl/2 mouse embryo fibroblasts. In: Microsomes, Drug Oxidations, and Chemical Carcinogenesis, vol.
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From page 299... ...
Oncogenic transformation and mutation of C3H/lOTl/2 clone 8 mouse embryo fibroblasts by alkylating agents. Cancer Res.
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Biochemical characterization of fluoropyrimidine-resistant murine leukemic cell lines. Cancer Res., 42: 965-73.
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From page 301... ...
Oncogenic transformation of C3H/lOTl/2 C1 8 mouse embryo fibroblasts by inhibitors of nucleotide metabolism. In: Genetic Consequences of Nucleotide Pool Imbalance, ed.
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From page 302... ...
302 BIOGRAPHICAL MEMOIRS PATENTS 1957 2,802,005 (August 6, 1957~.
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