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FILE NAME: Talc (TALC) DATE: 1986 DOC#: TALC028 DOCUMENT DESCRIPTION: Journal Article - Demonstration of the Migration of Talc from the Vagina and Posterior Uterus to the Ovary in the Rat <fc&. M im m ii --saHiti^ii<niflBWMlrtirlMigftaraf*iB8I8i^Bisiirirt- ' "m -TdOr f " " ty jumenta! m ,,a i ounaation no del Ducc 8 Milan, Italy Hermann ssah Medical School ilem, Israel rsity o f Medicine and itistry of New Jersey rk, NJ 07103 Jer can Health Foundation 43 St. York, NY 10017 aguchi nal Institute of istrial Health saki, Japan >r by any means, elecstorage and retrieval is journal indicates the or internal use, or for ndition, however, that ter, Inc. (27 Congress :tions 107 or 108 of the i, such as copying for ollective works, or for no fee code appears on e n v i r o n m e n t a l r e s e a r c h 40, 247-250 (1986) The Demonstration of the Migration of Talc from the Vagina and Posterior Uterus to the Ovary in the Rat W. J. Henderson, T. C. Hamilton,1 M. S. Baylis, C. G. Pierrepoint, and K. Griffiths Tenovus Institute for Cancer Research, University o f Wales College o f Medicine, The Heath, ' Cardiff CF4 4XX, Wales : Received May 15, 1984 ' Talc particles placed in both the uterine migrate to the ovary and become localized cavity within and the vagina its substance, ocf the 1986 rat were shown Academic Press, inc. to INTRODUCTION ' The presence of talc particles deeply embedded in ovarian and cervical benign and malignant tissue was reported by this Institute (Henderson et al., 1971). Posi . live identification of the particles was achieved (Griffiths et al., 1973) by replica i ting the surface morphology of tissue sections (Henderson, 1969) and analyzing j the X-ray emission spectra of extracted foreign materia! with an electron micro , scope microanalyzer (EMMA, A. E. I. Harlow, England), j Direct communication between the external environment and the peritoneal cavity exists in the female via her genital tract. It has been demonstrated that the 1 injection of a suspension of talc beneath the bursa of the rat ovary was followed J by ihe development of large ovarian bursal cysts, with associated epithelial changes not inconsistent with the histological picture of premalignancy (Hamilton el a!., 1984). It was, therefore, of interest to see whether talc placed in the lower part of the female genital tract of the rat would migrate anteriorly to the ovary. MATERIALS AND METHODS In a pilot study eight female exbreeder Sprague-Dawley rats 7.5 months old i were used. Under light ether anesthesia a speculum of an auroscope with the lens j removed was introduced into the vagina and the cervical os illuminated. A Portex catheter (o.d. 0.75 mm) was passed a distance of approximately 2.5 cm into the j cerv ical canal from the vagina introitus and a suspension of talc (100 mg/ml) in phosphate-buffered saline (PBS) introduced (vol 250 p.1). The animals were di- | vided into two groups of four. Group I was sacrificed 5 days following intra uterine instillation of the talc suspension and their ovaries were removed. The | animals in Group II received further uterine instillations 6 and 15 days after the : initial treatment. On Day 20, two rats from this group were killed and their ; ovaries removed. The remaining two rats received further treatments 22 and 30 days after their initial treatment and were sacrificed on Day 49. i i 1Present address: Medicine Branch, Division of Cancer Treatment, National Cancer Institute, Building 10, Room 12 N226, 9000 Rockville Pike, Bethesda, Md. 20205. 247 0013-9351/86 $3.00 Copyright 1986 by Academic Press. Inc. All rights o f reproduction in any form reserved. The material on this page was copied from the collection of the National Library of Medicine by a third party and may be protected by L 248 HENDERSON ET AL. The ovaries from each animal were combined and subjected to an ashing pro cedure as described previously (Henderson et a i , 1978). Essentially this process removes organic matter by heating the organs to 550C in the incineration chamber of a horizontal tubular muffle furnace in a stream of oxygen (250 ml, min/500 mg wet wt for 5 hr). The ashed material was then suspended in distilled water (50 p.1). Aliquots (10 pd) were pipeted onto carbon-coated electron micro scope grids and the water was evaporated. A further carbon coat was applied in vacuo to stabilize any particles and to dissipate heat and electrostatic charge gen erated by the concentrated electron beam prior to examination with the EMMA. Twelve Sprague-Dawley exbreeder rats of a similar age to those used in he experiment described above were divided into two groups of six. Group I animals were firmly held and the louver of a 1-ml disposable microjet 501 TB syringe was introduced into the vaginal orifices and 250 pd of a suspension of talc (100 mg ml) I in PBS was deposited into the vaginas. The animals in Group II were treated similarly except that 250 pul of PBS was substituted for the talc suspension. Two i animals from each group were sacrificed 24 hr, 48 hr, and 4 days, respectively, I following initial treatment. Their ovaries were removed and treated similarh to those described in the first experiment. MIGRA RESULTS Particles of talc were identified in the ovaries of all the animals that received intrauterine talc and in the two animals that received intravaginal talc killed . Iter 4 days (Fig. la). X-Ray analysis (Fig. lb) confirmed the chemical constitution of talc. No talc could be demonstrated in the group of rats that had received PBS intravaginally or in those animals with intravaginal talc killed after 24 and 48 hr. Fig . I. (a) Particles of talc re mi-pension of talc into the pos particles showing the 3:1 ratio o' DISCUSSION Birfringent particles were first noted to be present in human ovarian carci The association of talc nomas by Graham and Graham (1967) who postulated that these particles might (Tichtman et al., 1946) anc be asbestos. Subsequent work at this Institute identified talc in ovarian cancer stromal structure may leai tissue but not asbestos (Henderson et al., 1971; Griffiths et al., 1973). The ease of Carcinogenic activity o; migration of particulate material from the vagina to the peritoneal cavity (Venter presence in the environmt I and Iturralde, 1979; Iturralde and Venter, 1981) has been established. it under suspicion (Longo s The physiological mechanisms associated with translocation of particulate ma normal and malignant tT Is tmeraimalmwailtiahninsptheecigese.niTtahletcrahcetmaicreal unnaktunroewonf bthuet apraertpicruolbaateblwy oouplderantoitveapipneamrotsot oCvlaarmiaenr ectanalc.er(19an82d) tshueggues alter its ability to be transported through the genital tract and does not elicit any exposure to talc to the incl II selective mechanisms. Indeed it is accepted that retrograde flow of menstrual nelson and Mokronosova. % products into the peritoneal cavity via the Fallopian tubes is not an uncommon ical properties of talc is ac i f4i finding by laparoscopy at the time of menstruation. The rhythmic muscular con 3 tractions of the uterus that occur spontaneously and the illicit currents estab '-'r imer, D. W., Welch. W. R., S lished by the epithelial cells of the genital tract may contribute to the transloca talc. Cancer 50, 372-376. a tion process. aeli, G. E., and Newton, M. (19: * Talc is widely used in the cosmetic and pharmaceutical industry and has been ^ tive tract. Fertii. Steril. 12, i 9 associated with the use of certain forms of barrier contraceptives. Many women Liruham, J., and Graham, R. (19( apply talc to their perinea and some to their sanitary ware (Cramer et al., 1982). Griffiths, K., Henderson, W. J., new analytical approaches. I in ashing pruY this process incineration 'gen (250 ml in distilled -coated electron miern>on coat was applied in lectrostatic charge gen lation with the EMMA ge to those used in th_ of six. Group I animals )jet 501 TB syringe sion of talc (100 mg.-mb Group II were treat id -e talc suspension. Tv.,, id 4 days, respective!', . tnd treated similarly to MIGRATION OF TALC IN RAT GENITAL TRACT 249 animals that received vaginal talc killed afiei hemical constitution m that had received Plis lied after 24 and 48 In Ft 1. (a) Particles of talc recovered from the ovary by oxygen ashing following instillation of a suspension of talc into the posterior genital tract of a rat ( 10.000 x ). (b) Spectral analysis of the particles showing the 3:1 ratio of silicon to magnesium characteristic of talc. , human ovarian etna it these particles mig.;: talc in ovarian cane.; ' al., 1973). The ease m ritoneal cavity (Vcntv; established, ition of particulate m., ibly operative in m et :e would not appear to and does not elicit an\ ade flow of menstrual s is not an uncommon nythmic muscular con ' illicit currents estabibute to the transkv .1- industry and has been eptives. Many women (Cramer et al.. 19S2>. The association of talc with formation of granulomata is well documented iLkhtman et a l , 1946) and it may be speculated that disruption of normal ovarian stromal structure may lead to disturbances in steroid hormone metabolism. Carcinogenic activity of talc has not been established although its ubiquitous presence in the environment and its elemental similarity to asbestos has brought it under suspicion (Longo and Young, 1979). However, it has been found in both j normal and malignant tissue and its precise role remains unclear, although Cramer et al. (1982) suggested that a relationship between increased incidence of j ovarian cancer and the use of talc existed. A long latent period from the initial exposure to talc to the induction of malignant change has been postulated (Kats nelson and Mokronosova, 1979), but until a greater understanding of the biolog I ieal properties of talc is achieved further speculation is unjustified at this time. ! t REFERENCES j Cramer. D. W., Welch, W. R., Scully, R. E., and Wojciechowski, C. A. (1982). Ovarian cancer and J j talc. Cancer 50, 372-376. E., and Newton, M. (1961). The transport of carbon particles in the human female reproduc ! live tract. Frtil. Steril. 12, 151-155. Graham, J., and Graham, R. (1967). Ovarian cancer and asbestos. Environ. Res. 1, 115-128. Grithihs. K., Henderson, W. J., Chandler, J. A., and Joslin, C. A. F. (1973). Ovarian cancer: Some new analytical approaches. Postgrad. Med. J. 49, 69-72. ? 250 HENDERSON ET AL. Hamilton, T. C., Fox, H., Buckley, C. H., Henderson, W. J., and Griffiths, K. (1984) Effects of t ri on the rat ovary. Brit. J. Exp. Pathol. 65, 101 -106. ` " Henderson, W. }. (1969). A simple replication technique for the study of biological tissues by electron microscopy. J. Microsc. 89, 369-372. Henderson, W. J Joslin, C. A. F , Turnbull, A. C,, and Griffiths, K. (1971). Talc and carcinoma f the ovary and cervix. J. Obstet. Gynaecol. Brit. Commonw. 78, 266-272 Henderson, W. J., Melville-Jones, C., Wilson, D. W. and Griffiths, K. (1978). Oxygen incinerate, and electron microscope micro-analysis of mineral particles in biological tissues. J. Histocho, Cytochem. 26, 1087-1093. ' Iturralde, M., and Venter, P. F. (1981). Hysterosalpingo-radionuclide scintigraphy (HERS). Sew ,, yitcl. Med. 11, 301-314. Katsnelson B^A., and Mokronosova, K. A. (1979). Non-fibrous mineral dusts and malignant n- mours. J. Occttp. Med. 21, 15-20. ' Lichtman, A. L., McDonald, R., Dixon, C. F, and Mann, F. C. (1946). Talc granulomas. S,trV necol. Obstet. 83, 531-558. Longo, D. L., and Young, R. C. (1979). Cosmetic talc and ovarian cancer. Lancet 2, 349-351 Venter, P. F., and Iturralde, M. (1979). Migration of a particulate radioactive tracer from the vagin, io tne peritoneal cavity and ovaries. S. Afr. Med. J. 55, 917-919. ENVIRONMENTAL RESEARCH Critical Conce Humans [ Kji N o g a w a , R Ik ik o T suri Department o f Hypie Cadmium (Cd) was d Subjects consisted of 51 controls ages between 3 were 35.2 p.g/g wet wt values for the control gr kidney cortex Cd were a The kidney cortex conci trations up to approxim. increase in kidney corte' 200 p.g/g. The lowest liv around 30 p.g/g. The criti exposed to environment; W et Wt. e, 1986 Academic Pr Chronic exposure to i (Friberg et al., 1974; No considered as the majoi seems to be more sensiti 1974, 1979). Kidney damage consi /.. 1979; Buchet el al.. increase in total protein ocids in the urine, a de (FiTRP), decreased creat berg, 1950; Piscator, 196 Kjellstrom et al., 1977; S 1979b, 1980a, b, 1981c; P and/or glucosuria as well inhabitants of different C gawa et al., 1975, 1980b matsuetal., 1980; Koba\ tality among Cd-polluted (Nogawa et al., 1981b). T intoxication.