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Immunotoxicity of arsenic
772
Abstracts
130. E V A L U A T I O N OF I M ~ O T O X I C I T Y OF COMBINED PESTICIDES 1N MICE. D. Flipo, J. Bernier, K. Krzystyniak, M.Fournier. D~partement des s c i e n c e s biologiques, TOXEN, U n i v e r s i t ~ du Qu@bec & Montreal, C a n a d a .
We have p r e v i o u s l y s h o w n that s i n g l e e x p o s u r e to s e l e c t e d p e s t i c i d e s a f f e c t e d h u m o r a l r e s p o n s e . In this study, the e f f e c t s of e x p o s u r e to c o m b i n e d p e s t i c i d e s of k n o w n i m m u n o s u p p r e s s i v e ( d i e l d r i n and c a r b o f u r a n ) or s t i m u l a t o r y p r o p e r t y (malathion) w e r e m o n i t o r e d . Primary h u m o r a l r e s p o n s e to s h e e p e r y t h r o c y t e s (SRBC) was e x a m i n e d at d a y i0 a f t e r ip e x p o s u r e of C 5 7 B I / 6 i n b r e d m i c e to the mixture. In parallel, the c a p a c i t y of m a c r o p h a g e s to p h a g o c y t o s e f l u o r e s c e n t b e a d s and p r o c e s s an a n t i g e n s u c h as a v i d i n w e r e a l s o e v a l u a t e d . It w a s s h o w n t h a t e x p o s u r e to the m i x t u r e of two p e s t i c i d e s of s u p p r e s s i v e and s t i m u l a t o r y potential respectively, p r o d u c e d e f f e c t s c o m p a r a b l e to the a d d i t i o n of the k n o w n a c t i o n s of e a c h i n d i v i d u a l p e s t i c i d e . In c o n t r a s t , no a d d i t i v e e f f e c t w e r e o b s e r v e d u p o n s i m u l t a n e o u s e x p o s u r e to two i m m u n o S u p p r e s s i v e p e s t i c i d e s . S u p p o r t e d by NSERC, F O N D A T I O N UQAM and TOXEN.
131. IMMUNOTOXICITY OF ARSENIC -Immunological changes observed in the workers contacting with arsenic and in the mice exposed to it, and t h e i r possible mechanismsT a k a h i k o YOSHIDA,I T a d a k a t s u SHIMAMURAz and S a d a y o s h i SHIGETA 1 D e p t . Occup. H e a l t h and E n v i r o n . M e d . , S c h . M e d , , T o k a i U n i v . ~ and Dept. Bacterioi. I m m u n o i . , Sch. U e d . , S h o w a U n i v , 2 JAPAN We o b s e r v e d that t h e PHA r e s p o n s e s o f p e r i p h e r a l lymphocytes were enhanced in the semiconductor w o r k e r s who had been e x p o s e d t o a r s e n i c as d u s t , b u t d i d n o t show a n y c l i n i c a l symptoms. Furthermore, i t was f o u n d t h a t t h e a n t i g e n i c (PFC i n v i t r o ) and m i t o g e n i c (PHA and LPS) r e s p o n s e s o f t h e l y m p h o c y t e s f r o m t h e m i c e e x p o s e d t o a r s e n i c was a l s o e n h a n c e d a t low dose exposure. H o w e v e r , t h o s e r e s p o n s e s w e r e t u r n e d t o be s u p p r e s s e d a t h i g h dose e x p o s u r e . The r a t i o of Th/Ts cells increased i n a d o s e d e p e n d e n t manner. Further, i t was c o n f i r m e d that Ts p r e c u r s o r s w e r e more s e n s i t i v e to arsenic than other immunocytes. A t low d o s e exposure, ls cells were impaired first. As t h e d o s e i n c r e a s i n g , all the immunocytes including Th c e l l s w e r e damaged. So t h e immune r e s p o n s e s w e r e s u p p r e s s e d . This is the possible mechanism for the effects o f a r s e n i c on t h e immune s y s t e m .
132.
E F F E C T S OF I N T E R L E U K I N - 2 A N D I N T E R F E R O N - G A M M A ON H E A R T CONTRACTILITY. M a r i a M.E. de Bracco, Enri S. B o r d a and L e o n o r Sterin-Borda. I I H E M A - A c a d e m i a N a c i o n a l de M e d i c i n a and C E F Y B O - C O N I C E T , Buenos Aires, Argentina. We h a d p r e v i o u s l y shown that i n t e r l e u k i n - 2 (IL-2) increased the c o n t r a c t i l e tension of b e a t i n g rat atria, w h i l e i n t e r f e r o n - g a m m a (IFN-gamma) had the opposite effect. I F N - g a m m a i n t e r a c t e d with c h o l i n o c e p t o r s of the h e a r t tissue and enhanced the e f f e c t of c h o l i n e r g i c agonists. Thus, the negative inotropic and c h r o n ~ tropic effects of I F N - g a m m a (i0 units/ml) were p r e v e n t e d by p r e i n c u b a t i o n of atria w i t h 10-7M atropine. On the other hand, IL-2 (10 units/ml) e x e r t e d its positive inotropic e f f e c t through the b e t a a d r e n e r ~ i c pathway, since its action was b l u n t e d by p r e i n c u b a t i o n of rat atria w i t h 10-1M propranolol. The action of both l y m p h o k i n e s w a s p r e v e n t e d by incubation of atria w i t h the p r o t e i n kinase C H7 (10-6M) . A d d i t i o n of I F N - g a m m a before IL-2, r e n d e r e d the h e a r t tissue unresponsive to the positive effect of IL-2. Conversely, p r e i n c u b a t i o n with IL-2 abr o g a t e d the e f f e c t of IFN-gamma. These results indicate that the direct effects of lymphokines on the h e a r t can be the c o n s e q u e n c e of their interaction w i t h the s i g n a l i n g systems that are normally involved in the regulation of heart function.
Abstracts
130. E V A L U A T I O N OF I M ~ O T O X I C I T Y OF COMBINED PESTICIDES 1N MICE. D. Flipo, J. Bernier, K. Krzystyniak, M.Fournier. D~partement des s c i e n c e s biologiques, TOXEN, U n i v e r s i t ~ du Qu@bec & Montreal, C a n a d a .
We have p r e v i o u s l y s h o w n that s i n g l e e x p o s u r e to s e l e c t e d p e s t i c i d e s a f f e c t e d h u m o r a l r e s p o n s e . In this study, the e f f e c t s of e x p o s u r e to c o m b i n e d p e s t i c i d e s of k n o w n i m m u n o s u p p r e s s i v e ( d i e l d r i n and c a r b o f u r a n ) or s t i m u l a t o r y p r o p e r t y (malathion) w e r e m o n i t o r e d . Primary h u m o r a l r e s p o n s e to s h e e p e r y t h r o c y t e s (SRBC) was e x a m i n e d at d a y i0 a f t e r ip e x p o s u r e of C 5 7 B I / 6 i n b r e d m i c e to the mixture. In parallel, the c a p a c i t y of m a c r o p h a g e s to p h a g o c y t o s e f l u o r e s c e n t b e a d s and p r o c e s s an a n t i g e n s u c h as a v i d i n w e r e a l s o e v a l u a t e d . It w a s s h o w n t h a t e x p o s u r e to the m i x t u r e of two p e s t i c i d e s of s u p p r e s s i v e and s t i m u l a t o r y potential respectively, p r o d u c e d e f f e c t s c o m p a r a b l e to the a d d i t i o n of the k n o w n a c t i o n s of e a c h i n d i v i d u a l p e s t i c i d e . In c o n t r a s t , no a d d i t i v e e f f e c t w e r e o b s e r v e d u p o n s i m u l t a n e o u s e x p o s u r e to two i m m u n o S u p p r e s s i v e p e s t i c i d e s . S u p p o r t e d by NSERC, F O N D A T I O N UQAM and TOXEN.
131. IMMUNOTOXICITY OF ARSENIC -Immunological changes observed in the workers contacting with arsenic and in the mice exposed to it, and t h e i r possible mechanismsT a k a h i k o YOSHIDA,I T a d a k a t s u SHIMAMURAz and S a d a y o s h i SHIGETA 1 D e p t . Occup. H e a l t h and E n v i r o n . M e d . , S c h . M e d , , T o k a i U n i v . ~ and Dept. Bacterioi. I m m u n o i . , Sch. U e d . , S h o w a U n i v , 2 JAPAN We o b s e r v e d that t h e PHA r e s p o n s e s o f p e r i p h e r a l lymphocytes were enhanced in the semiconductor w o r k e r s who had been e x p o s e d t o a r s e n i c as d u s t , b u t d i d n o t show a n y c l i n i c a l symptoms. Furthermore, i t was f o u n d t h a t t h e a n t i g e n i c (PFC i n v i t r o ) and m i t o g e n i c (PHA and LPS) r e s p o n s e s o f t h e l y m p h o c y t e s f r o m t h e m i c e e x p o s e d t o a r s e n i c was a l s o e n h a n c e d a t low dose exposure. H o w e v e r , t h o s e r e s p o n s e s w e r e t u r n e d t o be s u p p r e s s e d a t h i g h dose e x p o s u r e . The r a t i o of Th/Ts cells increased i n a d o s e d e p e n d e n t manner. Further, i t was c o n f i r m e d that Ts p r e c u r s o r s w e r e more s e n s i t i v e to arsenic than other immunocytes. A t low d o s e exposure, ls cells were impaired first. As t h e d o s e i n c r e a s i n g , all the immunocytes including Th c e l l s w e r e damaged. So t h e immune r e s p o n s e s w e r e s u p p r e s s e d . This is the possible mechanism for the effects o f a r s e n i c on t h e immune s y s t e m .
132.
E F F E C T S OF I N T E R L E U K I N - 2 A N D I N T E R F E R O N - G A M M A ON H E A R T CONTRACTILITY. M a r i a M.E. de Bracco, Enri S. B o r d a and L e o n o r Sterin-Borda. I I H E M A - A c a d e m i a N a c i o n a l de M e d i c i n a and C E F Y B O - C O N I C E T , Buenos Aires, Argentina. We h a d p r e v i o u s l y shown that i n t e r l e u k i n - 2 (IL-2) increased the c o n t r a c t i l e tension of b e a t i n g rat atria, w h i l e i n t e r f e r o n - g a m m a (IFN-gamma) had the opposite effect. I F N - g a m m a i n t e r a c t e d with c h o l i n o c e p t o r s of the h e a r t tissue and enhanced the e f f e c t of c h o l i n e r g i c agonists. Thus, the negative inotropic and c h r o n ~ tropic effects of I F N - g a m m a (i0 units/ml) were p r e v e n t e d by p r e i n c u b a t i o n of atria w i t h 10-7M atropine. On the other hand, IL-2 (10 units/ml) e x e r t e d its positive inotropic e f f e c t through the b e t a a d r e n e r ~ i c pathway, since its action was b l u n t e d by p r e i n c u b a t i o n of rat atria w i t h 10-1M propranolol. The action of both l y m p h o k i n e s w a s p r e v e n t e d by incubation of atria w i t h the p r o t e i n kinase C H7 (10-6M) . A d d i t i o n of I F N - g a m m a before IL-2, r e n d e r e d the h e a r t tissue unresponsive to the positive effect of IL-2. Conversely, p r e i n c u b a t i o n with IL-2 abr o g a t e d the e f f e c t of IFN-gamma. These results indicate that the direct effects of lymphokines on the h e a r t can be the c o n s e q u e n c e of their interaction w i t h the s i g n a l i n g systems that are normally involved in the regulation of heart function.