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/ Verb~d der Cigaretten-lndustrle, Nissenschaftllche Forschungsstelle ~.Isse'nsch.aftllche~~ Belrat, l~amburg, Cat-any / "SITZUN~ DES ~ISSENSC~F~LICHEN BEI~TS, August ~3) 1955 (Hinutes of the ~eetin~ o~ the Scientific Advisory Board o~ ~he Sc'ientlfic • ~esearch ~nstf~ute of the Ce~an Cigarette Industry Trade Assoclatlon~ August 13, 19~.) "" erband der Clgaretten-lndustrle~ Nlssenschaftll~he Forschungss~elle, Wissenschaftllch~elrat, Hamburg, ~e~any~ 21 pages, August 13, 196~ / I.~EDITED DRAFT The followlng is a rough Engllsh su~-~ary of sore s~atters of interest from the minutes. (Page 4) ~ITPATE PRO~RAH Suv~ary of investigations in the green house: 1. The nitrate content in the tobacco plant can be controlled by regulating the a~ounts o~ nitrate (HO3++I~o3+++). A smaller dosage does not necessarily entail a substantial lowering of the crop yield. Our observations sho~ that the nitrate content iu the leaf of a liv~n~ tobacco plant can J~ between 0.01 and 6~) and in the stem between 0.I a~d 17~. ~oveve~ the uatur~of the plan~s sl~differs noticeably• 3. Under the conditions ~iven ~onium nitrogen cannot be used as an only source of nitrogen. The plants stop gro~Ing. 4. It sce~s that'the presence of larger a~ounts of ~anzanese does not always cause nitrate reduction. The expected correlation beco:~es distinct only in a relatively late stage of the harvest. (Table 8) S. It could be con~ir~ed that nitrates are stored preferably in the bottom leaves. .... • "! Redacted i Pr,v,leged a-tena ,

-2- "T r-=- The st~cker and steu tissues see~ to b~ n p~'efe~red pl~|¢e'f~ ~[trate storage. The leaf (lamina) itself is relatively Io~ in nltro~en. (Page 8) SI,OAN-I~ETTERINC-~t]STITtlTE Dr. Nebec infoms that he spoke a~aln to Hr. Schlenker about sending 50~00 cigarettes ~o Dr. Nynder. Fir. $chlenker agreed to send these cigarettes. However, Dr. |{ynder shall be asRed to inform the Forschun~._ ~stelle about results of his investigation with these cigarettes prior to publlcatlo~. Dr. Neber reports that Dr. Wynder could not detect a decrease in the tumor pro~otlng effect when using condensates from charcoal ~ilter-tlp cigarettes. Another scrles o~ e~:perlments sho~ed that the addition of nitrates to tobacco decreases not only the trace-amounts o~ polycycllc hydrocarbons~ but also the tu~or yleld.. Based on a further experi=en~and chemical analyses~ Dr. Wynder concludes that the tunor promoting effect is concentrated in the neutral fraction of the condensate. Dr. ~leber r~lnds that one year elspsed since the last ~0~000 the: he ~sks for the Board|s $1oan-~et tering-Zns titut e; regarding a ne~ equal sb~9=ent.s:~ount. Dr. Lipp and H~. Jodl abstainh( the re~aining =e~bers o~ ~he Bosrd~in ~svor. Dr. L~pp su~es~ to ~ls~ sbow contribution and also ~he contributions to the ~rebs~orschun~s- zen~r~ (Cancer Research Cen~er) In ~eidelber~ ss donations to scientific ins~i~u~es rs~her thsn research gran~s. (~s~e g) D~. ~OL~ The Boar~ is o~ ~he opinion ~h~ ~ore reliable i~[o~a~ton biolo~[cal ~igni~icance o~ ~he discussed ~races of Polon[u= 210 Is necessary before ~ur~her or =ore thorough snslytic~l s~u~ies sre ~srrs~ed.

(Page 12) FOI.LY A~ITOI'ATIC SI.'.OIIII:G I't..',CIIINE FOR PI~EPAP~:,TIO!! OF IJ.R(:.E ." .'JU.'~S . ~ CONn~SA1 ES. Dr. £[nenhorst tells thaC Hcss~s. Carugno and l-lil[[ar~s~n~ ~e~be~s of the Cosesta G~oup for Development of a Fully Aut~:~aLic S~okIn~ Hach~ne, vere l~ Hamburg on Ju~y 5~ [9~5~ and ~nspec~e~ ~h~ ~achine developed by Dr,'~l~=nho~st and collaborators. D~. Els~enhozst ~n[o~ed Pro~. Cuz[n about ~he developaent o{ hl~ ~achine. He asks vhe~her an a~te=pt should be =ade to oodl£y ~he r:achine ~urther Lo enable it to s~o~e to an exact bu~t-len~h, A~ p~esent ~he ~ach£ne s~oke~ a ~tandar~ n¥;~ber o{ The ~oa~d~s advice is that such a uodl~lcation is not ~o~ths~hlle because seok~ng a f~xed number o~ pu~£s is ~ore precise a~ a standard than the attempt to keep an exact length o[ the butt. Dr. El~enhorst In~or~s that one person could ;,~tend eight o[ the above uachines.

Attachaent 1, Pro~okoll o~ August l], 19~5 ~easibillt~ of Inhalation Experi-ents. v/th Cigarette S~oke D£scussicn: Prof. Dontenwlll, Board (AuBust 13, 1955) A. Smoke Inhalin~Apparatus. In the center oE the discussion wer~ a comparison between s~oke inhaling machines by Dontenwlll and by Harris and the possibility of ¢oabining both ~ethods. Apparatus by Rarrts~ It consists of the following three structural eie=~nts: i~ A 9ertical manifold holding 12 cigarettes simultaneously. A ~l~lfig Cha:~b~r~abdve the ~anifol~where the smoke is ~ucked ~nl d{lute~ in p~opo~tion 1~39, and then blown into the smoking ~6~partnent (Par~ ~), ~, A in6kiug 66apartnent~ about ~0 c=. long, with a pressure relief valve At its outer end. The tube has on each side lO conical openings where small uetal cages with the mice are set up. l~enty nice ake exposed once a day to th~ smoke of 12 cigarettes (duration approx. 12 minutes). According to Barris and ~egroni the aaount of suoke absorbed is estimated by detenaining the nicotine content the lung of the uouse. Apparatus. by Dontenwill. ~he following items arc significantly different ~rc~a the arrangement in Che previous apparatus: 1. Two cigarettes for every 18 hamsters are fed into the =anl~old, ~. ~he total tin~ of exposure is 4 x 40 uinutes daily, up to 32 cigarettes/ day/8 animals,. i

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-3- "Pets frequently develop broncho-pneu~,onln a~e~ stroking." M~reover, there is no nucous secretion In the bronchial tract of rats. I~ the case of ~Ic~, bronchloles are l~kewlse absent in the resplrat~ry .tract. In addltlon~ ~Ice have a tendency to develop adeno=ata. The adeno~atosls of the ~ouse lung is controlled to a large eztent by hor=onal and genetic factors. The V~A-t~odcl of adeno=a ceils corres- ponds to the V!~-~odel of norual cells. Thls indicates that, strlctly speaking, ve do not have ~allgnant degeneration. Prof. Donten~,£1[ feels,. therefore~ the lung adenoaatosls o~ the uouse to be insufficient as an indicator for investigations of cancerogenlc ~ubstances. ~hcn the enhanceaeng o~ the spontaneous rate o~ adenoaata is used as crleerlon~ investigations o~ the mouse lung are, h~aever, suitable for'teselng o£ a co-factor. ~hen tests are evaluated one could then only speak o£ a "tw~or-pr0=oelng" ef[ect. 3. The respiratory trac~ of the hanster £s ~ore readily co~parable to conditi¢ns present in huuans. There are bronchIoles and also =ucous ~ecre~ion. In'additlon~ after treatment ~Ith cancerogenlc ~aterlals, the hamster develops squs~ons-ep£thelial carclnonata. The adeno~a • . rate is extre=ely lo~ (about 1X). Hamsters are relatively resistant to infectious diseases of the lung and to other spontaneous diseases. In the case ~here larger groups of ha:tsters are needed, the care o£ the animals does not represent too big a difficulty. Increase o£ Yield of Exoerioentally Produced l.un~ T~ors. To date, vhen ~pplylng cigarette s~oke only, the =axlnun yield o~ lungtu~ors in the s~oking experluen~;by Essenberg, Leuchtcnberger, Dontenvlll~ Co

and others, vas 0.5-L.5£. -4- Such a yiel~is not sufficient ~or ccm.paratlve evatustlons of .the effects of canceroccnlc substances. There° £or~, one should consider ~ethods vhlch vould lead to a higher yield of t~mors in the tunes of test animals. .. Pc~slbly~ a belo~ threshold dosls of a kn~¢~ cancerogenlc ~aterlal could be added and then the ~oke analyzed for co-cancerogenic properties. ~he order of nagnttude of the.yield of lung tuuors at such a co=bination can be expected to be 2OZ. Pro£. Oontenvilt refers to papers'by Cegber who produced lung tuoors by applying a nlxture of active and inactive cerium fluoride and could observe then a very exact correlation between the doris mad che effect. According to experinents by Ceuber~ ttmors can be rarely expected at a dosis of ~bout 100 tad. She above experlnental coder could~ possibly~ be produced by decreasing so:sewhat the dosis and by applying cigarette suok~ at the sane Prof. Dontenwlll viii perforn in ~lunich preliuinary experiments by irradiating the chest of test animals.with a dosls of 500 tad. This rill be done in order to eliminate a disadvantage of a, perhaps, insufficiently uniforn distribution of radioactive energy over the tung of the artiest. Prof. Dontenwlll ~eels that it is not coo advisable to apply nltrosanines and smoke conbined. ". 1-27-55