Offi.-ce Memorandum-                        UNITEI5 STATES  GOVERNMENT
      TOA:                                                           DATR:  4  August   1954
      FIO)D
      SuBJwr:    Kethylcholanthrene
                       The following  are brief notes on Hethyleholant@,rene, in response
                 to vour request of   August2 3, 1954.
                 Literature:  George   Wolf,.AS3istant Professor, University     of Illinois.
                              "Chemical  Induction   of   Cancer"
                                                                  1953. see esp.  p.29.,44  etc.
                                Bk means  of  a  special  genetic technique, Strong,
                                J.N.C.I.5s 339s 1945 induced    tumors  with   met2tqlcholan-
                                threne in marw different tissues.
                                Methyl Chol@nthrene is a good initiator (high tumor incidence)
                                and a good promoter (short..latent period) -P-85 Wolf.
                                Hartwell:  Survey  of  Compounds  tested  for   Carcinogenic
                                properties PHS: 149         National Institute Cancer
               2                 E. C. HUBER:  Public Health Report Suppleftent 209, 1948
                                on Enviromental and Occupational Cancer.
                                National Institute Cancer
                                Louis F. Fieser and Mary Fieser:  Natural Products related
                                to Phenanthrene               .  .9             llethyl
                                                   3rd edition 1 49.. 2p. 159:
                                cholanthrene was  foui-A  capable  of  initiating  malignant
                                growth in test animals by Gel-tera3 Z. physiol, Chemie
                                214989s 1933.
                      'Rethylel-,olanthrene is now recognized as probably the most potent
                  known carcinogen in the production of tumors of various types.
                       If this 2hydrocarbon can be produced in the laboratoz7 by         chemical
                  transfonnations of normal constituents of the human orrar%Lsm.,     it  is
                  possible th.,.t the substance may arise in the bod,.r  through  a  process  of
                  abnormal  metabolism  -  and  initiate  cancer.
                       The degradations of desoxycholic acid (one of the normal con-
                  stitue2nts of liuman bile), cliolic acid " cholesterol (a substance in
                  all tissues of the body) all  involve  lovi-yield  pt,-rolytic  reactions;
                  they have not been effected under anything approaching physiological
                  coiiditions; careful processing of cancerous tissues and urines has failed
                  to estab3.iqh the presence of metlWlcti6lanthrene.
         8              There is thus  no  evidence  that  this  or  other  hydrocarbon  careino-
                  gen plays &rW role in the etiology of hman cancer.

                      On the other  hand                QC
                                          present  evide  e does not exclude such a
                  possibility.  Every mimte amount of motbyleholanthrene could produce
                  a few mmli nant ce3.1s; these - by ceu-division and without.
                      Further stimulation from the initiating agent    could lead  to  a
                  p2alpable cancerous proliferation after an induction   period during
                  which the initiating agent may have been el-inmnated  from the system,"
                  SOURCE:  3-Methyl-Cholanthrene:.  4383 Cat.  Chemical  Cpds.   Fischer
                           Scientific Co.   7722 Woodbury,  Silver Spring, Washington, D. Co
                             Price:  1/2  g. $4.40
                     2                   l.g. $8.25
                                                                                                    L
                    Carl Max 14asselmann and linns Otto Johne in Arch. Dermato    Syphi3.is
                    188.9 693-707p 1950 reported primar7 multiple  skin  carcinoma  with
                    simultaneous tertiar-y syphilis.                      %
                    Distur2bances of the cholesterol metabolism., presene in syphilis cases
                  of long standing, as well as cancer cases are   discussed with respect to
                  the cliemical reaction between the physiologice-1 substances:  cholesterol,
                  bile acid and desoxycholic acid, and the cancerogenic substsnces cholan-
                  threne and mettqlcholanthrene. -Both Huber and HartvieU appear ver7
                  knowledgable9 and are connected  with  the-National  Institute  Cancer.