Document 6Y52gMJYqJ5DLBaLGD1Mw1JR

AIA-87 | Xarch 15, 1943 i I j Dr. Icdvig Sektoen, Chairman. Committee on Cancer Research National Cancer Institute 3ethesda, Xaryland . Dear Dr. Sektcem . Is analyzing the results or a recently completed Inhalation experiment os asbestosis, I vas startled to discover that a snail group or 11 whit* aloe that had been * r*a*t * aabes tos dost frca 15 to 24 tenths aheved an excessive incidence (81.c2) oT pulmonary cancer. This experience vas quite at variance vlth th results Is.all our previous long-taro dust exposures which were ssmarlted and published by Tcrvald and Xarr is the American Journal or Pathology, January 1933. I would have attached little significance to this recent rinding because or the email number or animals involved, bat Tor the ract that the literature now contains sons 10 reports or pulmonary cancer Is cases of facnan asbestoals. Even these I have heretofore attributed to selection or material as we have found no cases or pulmonary tumor is survejs or employed asbestos workers. However, Gloyns, Xerevether and other English observers contend that asbestoe has a specific carcinogenic action on the lunge. The question la of considerable importance is indus trial medicine- because of the associated compensation aspects and from & scientific: view point. It Interests me a great deal. la view or this recent finding I have reanalyzed the results of a large number of dust Inhalation experiments that ve have carried on during the past 25 years. The incidence of pul monary tumors Is shown In the appended table. It would appear that, except in alee, tumors have been generally uncommon in the" strains-- of different species that we bad used. Guinea pigs have shown oc casional adenomas of the lung whose incidence is not influenced by dust exposure or by the type of dust involved. However, in white ' \ mice that survived for 15 or core months in our dost rooms, various \ forms of long tumors were much more frequent. The average incidence 'Of such tumors in a group of 143 nice exposed to 4 different qpartz- ccataiming dusts vas 13.82 but this appears small in contrast to *his incidence of 81.82 in the asbestos mice. In 51 younger nice that died or vere killed after exposures of 10 or 11 months there s only one Instance of pulmonary tumor. Therefore, either age or ......'atlon of dust exposure muat be important. PRODUCED . JM - 83 01025S * AIA-87 Dr. Ludvig Sektoea -a Xarch 15, 1543 Hona of thsse experizenta was planned to study c&ecinogsnic effects. HIce were only used as there vaa soace In the dust mens and many of these animals that died after short exposures vere discarded without autopsy as they could not have developed a sufficient amount of dust reaction to be of Interest. The strain of nice kept In the laboratory has changed fron tine to tine by Im portation of nev 3tock. At one tine vs did procure from Dr. Baud Sly s=e cancer susceptible ate oh but as these an.lan.Is failed to react to Inhaled quartz ve lest Interest In the subject. Chvdonsly under such conditions, the results with asbestos nsan nothing but In vlev of the considerations which. I have cited. Z believe they should be cheched. A decisive answer to this question would be of real practical value. ?rosr what we have learned about the action ef a3best!fom cinerala In the living tody, I would sot be surprised, to discover that their carcinogenic effects are dif ferent fros those of ether slnerals- Their crystallographic structure Is mnlqua- They apparently act as mechanical irritants rather than chemically as is the ease with quartz and other fame of free silica. Ca crushing or grinding, asbestos fibres loose parctically all their irritating capacity; quartz on the other hand, becomes nore. Irritating as the particle also decreases. Asbestos provokes fibrosis only in the lungs of certain species; quartz excites such reaction in any organ of an7 species of animal that ve haTe tested. Asbestos seens to have no specific action upon pulmonary eplthellus but in soae species, it cause-an unusual type of diffuse fibrosis which cocpresses and distorts the epithelial-lined respiratory bronchioles but often fails to obliterate them. However, this aechaaisa would sot appear to be the one responsible for the mouse tumors for this la one of the species which develops no fibrosis on exposures Possibly, the lack of reaction Is due to stxp-erior'Upper respiratory, protection against inhaled.foreign bodies,* The., lungs of aloe, exposed to asbestos dust for two years reveal relatively few fibre and all of these are short and eoated to forn that peculiar . structure* known as the asbestos body. : In order to verify our accidental discovery of pos sible carcinogenic action of fibrous asbestos, I would like to repeat :he mouse inhalation experiment under properly controlled conditions. * would breed a large number of cancer susceptible aloe, splitting oh litter into three groups and keep a record of the ages of each. ~ 1 third of tha offspring would be kept in a normal atmosphere as a .: -trol; another third would be exposed to quartz du3t as a second 'rcl and the other third would be exposed to asbestos dust. Ve PRODUCED JM-83 00010235 AIA-87 * 3r. Lndvlg Sektoen Harch IS, 1343 Yould at tespt to obtain 5C0 nice for each group. The expo aura a would a;r psrently have to be continued for IS to 24 nonths. Cur routine In such experlseata provides for dusting: S hours a day, 5 days a week. 1 Ve hare all the necessary equlpsent for such ex- perlrents and a trained laboratory personnel, rusda are lacking hcverer. Cur prerloua study of aabeatoais vhlsh continued for a period or 7 years was financed by the Aabestca Association. Since this group of nacsfacturers has already invested |3C,CC0, I cannot ash then for further contributions. 1 discussed the natter vitk Ur. Rhodes at the Hencrial Hospital who favored and vaa of the opinion, that It van worthy or consideration by your consittee. I as therefore applying for a grant of *5,0CG to cover the cost or the first ysar'a expense. .. ' ,' ... - ' X had told Sr. Bhsdea that 1 would be willing to do the entire experirsnt for this ascent and ordinarily Z should. How ever, on ey return fsva See Tort, I found two proposals for lnvestiga- tlons or other iaduatrtal dusts each or which yield the Laboratory #3,GCO a year. As X have only tvs dust rooss at the present tine free for nev work, X cannot afford to tie up one of then for two years for half the accost. ' . yon be favorably Impressed with this proposal X would appreciate any arltiaissa or suggestions. - Sincerely yours, - LTOiRHB y-Ss"9i" Director 00010236 PR00UCE0 JM-83 010255