Document mmd0MOpYvRkD4pLy9z38Y6mOZ

6 fsATUHE VOi 243 . Jn >. . , 1 Wikknihal, K. J.. Prac. /*>-,;. .v-. 2<i7. u n> -i * Wtidcnihal, K. J.. / Appl /'*'/.. 30. I': M'/7; * WiUcnthal, K. J., Put. Pk)\n>/. .V**.. 217, wi|'7m 4 WiUcnthal, K. I.. Arne*. J l*A>x.l. 221. 2 k uv\, * Hughes, O. M.. and l.ongmorv, IV II.. Salute, 2.15 . . .'*7:, * Loflgmore, D. U.. and Hughes. I). M.. Nm-e, 2M. *> i ,'/7;( ' Nagkr, J., and Longmore, D. B., Solute, 242, 197 <iv71, ST00 9 5 7 I 4 Penetration of Asbestos through the Digestive Tract of Rats Mesotheliomas of the pleura and peritoneum1 J hav,, r<k., linked with the inhalation of asbestos fibres. Wc i.avc that asbestos fibres arc present in drinking water, hecr. w.r..; nd other beverages. Asbestos fibres can penetrate the nuiu'w of the stomach and intestine* and Telischi and ttubcnsu.ne* have found asbestos material in a gastric carcinoma. O<o* .* nd Jagatle*, reporting on mesotheliomas of the pleura c. -.j by asbestos, noted that asbestos particles were ss<Jdy do. buted in various tissues. They suggested that part.cics migrate from the lung through the blond and 1>i.,pr. . system to all parts of the body. In the light of these rvpor. we surmised that asbestos consumed orally can pass tiuou the gut into the blood stream and accumul. ic in varies u- ww To determine if this is the case we injcvicd a saspcim n .. asbestos libra into the stomachs of rats. The susp.r. . was prepared by shaking 2.3 g of chrysottle asbestos (Jnn... Manville No. 7RF02) in 300 ml of water in a fra in. cylinder. The suspension was allowed to settle for .to . and the top 230 ml, which contained about 9.4 * IGV d r<>,, fibres ml-1, was drawn off. Most of these fibres are G 2 2.0 pm long (Fig. 1). To ensure that fibres passed throu -h the digestive tract without rats inhaling any of then, i asbatos was introduced into the gastrointestinal iru opening the abdomen under anaesthesia and injecting .... fibres directly into the stomach. Two to 4 d later ;ne ,..ts were killed and blood and tissues analysed for asc.Mo-. t.-> ensure that any fibres on the rat nair couiu not coi.umin. c the organs removed during surgery, the rats were fir^t thor oughly vacuumed and washed with double disiilleu water methanol. During the removal of n'ssues wet towels we, placed over the animals and around the incisions Union* taminated blood was drawn from the oroital sinus using a capillary tube. To avoid formation of excess ash, which iniei.ere examination of specimens under the electron microscope. ' ,, tissues were first solubilized with solucnc (Packard Instrume... Company); the fibres were then centrifuged down, wasn.-u with methanol and ashed as previously described4 The asn was taken up in 1 ml of distilled water which had been fil'c. ca through a 0.2 pm filter, and 5 pi of this mixture was drop.-v 1 Fig. 2 Ventricular rales of the control hearts compared with the first 22 d for the test hearts. on hydrophilic carboncoated electron microscope gr.^% supported on a ring peg. The grids were dried in a glass container (to avoid air contamination) under a ca seem reasonable to continue with further conventional clinical lamp and were examined at magnifications of 20. M0 -;.u trials. If a new drug is depressant to the foetal myocardium 80.000 with an electron microscope. The presence of chrysonk above a certain concentration, it would be unwise to exceed asbestos fibres was verified by electron diffraction. They were this in a subsequent clinical trial If the substance were to counted and the numbers corrected for dilution to determine affect only young, foetal hearts it might still be safe in late the number in the original i ml sample. Results of recovery pregnancy. of asbestos fibres from rats treated in this way are shown m We thank the Board of Governors of the National Heart and Table I. Chest Hospitals and the British Heart Fouhdation-for financial . Rata in group 1 were given 9.4* 10* fibres (I ml) and xifiau support. Miss D. M. Hughes and our colleagues for help and 2 d later; those in group 2 received 94 x 10* fibres and were Dame Honor Fell arid Kern Wildcatbal for encouragement. killed 4 d later. No asbestos fibres were detected m the boo '- S. R. AsMsraoM of non-irgected rats..(controfs) but 4.63 x 10* g~" (a MatniiCa.iy D. B. LOnomom significant increase) were found in the first group. b'atio*al Heart Hcafital, > v., ... This is the first time direct physical evidence for tne presence Weumxeio*d Street, " . -of asbestos fibresinthe Wood hs been obtained. Four day* ?*,* *. 1 - * -^^^jPeatmeni^the amount of asbestos in the Wood of rats m - .t r.;i -f--- C grup 2 bad dropjMd to -I.IP* JO* f*` even though torse rat> RdKr*edJaAuary23;vftvin4 April 10, 1973. 3 '. ^lecovedleB titoW as mucb asbestos. Th indicates tlwt Wood DOW 02981 ST00957I5 NATURE VOL. 243 JUNE 1973 T*M 1 Numbers of Aabestos F*im Recovered Rem Twmj end Non-Treated Reu Blood Spleen Omentum Heart Brain Lungs Controls _meani* 0.00 2.33 0.67| 2.46 0.46 2.09 0.41 0.05 0.02 1.06 0.26 Croup mean 11 4.651 4.11 _2.74 1.02 0.49 0.17 0.311! 0.19 1.10 0.54 Croup mean 21 1.19 3.45 18.25 2.24 0.29** 1.74 0.77 1.20 7.79 0.40 0.11 0.26 * Average of five nu in *11 cates except where noted, t Animals injected with 9.4 x 10* fibres and tissues examined 2 d later. J Animalt injected with 94 x |0* fibres and liuues examined 4 d later. $ Standard error of the mean. H Four rats only. 1P<0.01; /*<o.os. (The figures in the table are fibres g"1 x JO-4.) can dear itself of the fibres. Tissues such as the spleen, heart and lung also seem to have, to a lesser extent, the ability to dear themselves of the asbestos fibres, as the figures obtained from rats in group 2 indicate. They are lower than those for group I rats even though they received a larger dose, but the tiuc$ had longer to clear themselves. Indeed, recent work in our laboratory with radioactive asbestos indicated that some tissues, such as the lungs, can reduce their fibre content by half in 2 d. This clearing action could possibly have quite an effect on the numbers of fibres found in the liver and kidney of the rats but unfortunately, because of the considerable amount of ash present in these organs even after soiuene treatment, we could not examine these specimens under the electron microscope. Another factor may contribute to the higher fibre count obtained for the organs of rats in group 1 compared with animals in group 2, namely, that there were four times as many fibres in the blood of rats in group 1. The residual blood in the tissues on removal from the animal would of course contribute to the total fibre count of a particular tissue. This factor could have created the anomaly in the fibre counts in brains. In the brains of treated rats this was about six times higher than in the controls, and the increase in fibre count is statistically significant for rats in group 2 but not, oddly, for rats in group l even though there were more fibres in these animals. The greater number of fibres per gram in the blood of rats in group 1 could be responsible for the larger standard error in the counts of rats in group 1 and therefore did not allow the values obtained to be significant The brain seems to have little ability to dear itself of asbestos fibres, but the omentum has even less. This tissue, which Fig. 2 Smalt bundle of asbestos fibres from the peritoneum of a rat. This bundle is at least 15 pm long. surrounds the small intestine, appeared to accumulate moM asbestos. Although the asbestos fibre content of the omentum* in rats in group 2 may seem rather high (one extreme count contributed to the high standard error) the omentum docs not seem to respond as do the other tissues. As well as having little ability to clear itself, fibre accumulation in the omentum may take place much more slowly than it does in other tissues. As the omentum consists partly of peritoneum and partly adipose tissue, asbestos fibres may enter the peritoneum by direct penetration of the intestinal wall. Concerning the prolonged retention of asbestos fibres in the onwmum in women asbestos workers, Keal* found a higher incidence of peritoneal cancer than of lung cancer. The amount of asbestos found in the tissues of the controls is higher than we had anticipated, considering the age of the rats and the number of fibres they might have consumed in their drinking water4. But we do not know how much w* in their feed or air. We have analysed tnc tissues of some people who died of natural causes and found somewhat similar levels. In one person there was twice as much asbestos in the brain as in the brains of our control rats and about one quarter as much in the omentum, but the omentum content was still higher than the brain. Most of the fibres found were about 0.2-2.0 pm long but flome measured 15 iun (Fig. 2) and one fibre in the blood of a rat was 23.55 pm long. We do not know how the fibres pass through the intestinal wall. Some long ones may pierce the gut like a needle, whereas pinocytosis may account for the absorption of the small ones. We demonstrated earlier the presence of asbestos fibres in air, snow, city drinking water and a number of beverages4. The experiment described here shows that fibres of a similar size administered into (he stomach of rats appear in the blood and accumulate in various tissues in the body. R. D. Pontefract H. M. Cunningham Food Research Laboratories, Health Protection Branch, Department of National Health and Welfare, Ottawa Racth rd November 30,1972; revised February 13, 1973. * Hourihane, D. 0. B., Thorax, 19.241 (1965). ' Hounhane, O. O. B . 4m. NY Arad. Sr/.. 132. 647 (,*>$i. ' 'Lynch. K. M., and Smith, W. A., Amer. J. Cancer, 24. ** < 1935) . 'fOmningham. H. M-, and Pontefract. R. D,, Notme. 232, 332 <19711. ' SeLkoff. |. J.. Churg. 1.. and Hammond, C., J. Amcr. hied. Auoe^ Iat, 674 (1964). -4'Tclachl, M., and Rubenstonc. A. I.. Arr*t. Pathol, 72 1961). MkCodwto* M. C. and Jagatic, Enrran. Met., 3, 391 (1V70). yUUsl, E. 1L, Lancer, u. 1211 (196011 DOW 02982