Effects of Opium Alkaloids on Mitosis and Dna Synthesis

Abstract

, we have surveyed serum and u r i n e from 3 1 normal b a b i e s , a t 1 and 5 days of age. Our r e s u l t s have demonstrated t h e pres e n c e of more than 50 o r g a n i c a c i d s , h a l f of which b e a r some r e l a t i o n t o t h e more common o r g a n i c a c i d o p a t h i e s . T h e i r sig n i f i c a n t r i s e i n serum and u r i n e a f t e r formula feeding sugg e s t s t h a t a comparable method of s c r e e n i n g f o r t h o s e o r g a n i c a c i d s known t o b e a s s o c i a t e d w i t h d i s e a s e , should p r e f e r a b l y b e a p p l i e d a f t e r 5 days of l i f e . The u s e f u l n e s s of s e r i a l a n a l y s i s was suggested by t h e presence of p o s s i b l y harmful m e t a b o l i t e s i n 3 serum a t day 1, w i t h normal l e v e l s a t day 5. These included i s o v a l e r i c , methylmalonic, benzoic, phenylacet i c and p-hydroxyphenylacetic a c i d s . We have a p p l i e d o u r method t o t h e i n v e s t i g a t i o n of 4 p a t i e n t s p r e s e n t i n g abnormal amino a c i d u r i a and found l a r g e amounts of t h o s e p h e n o l i c a c i d s c h a r a c t e r i s t i c of tyrosinemia and hyperphenylalaninemia. These f i n d i n g s s u p p o r t t h e r e l i a b i l i t y of o u r procedure i n s c r e e n i n g f o r metabolic d i s e a s e i n l a b o r a t o r i e s where mass spectrometry is u n a v a i l a b l e . This work was supported by t h e Medical Research Council of Canada, Grant MA 4767.BLASTS. Serge B. M e l a n~o n , Michel P o t i e r , Louis D a l l a i r e and Guy Geoffroy. Depc. of Ped. and Neurol., Univ. of Montreal and Ped. Research C t r . , Ste-Justine Hosp. Montreal, Que., Canada.We s t u d i e d a 20 months o l d French-Canadian g i r l p r e s e n t i n g t h e c l i n i c a l p i c t u r e of Tay-Sachs d i s e a s e w i t h p r o g r e s s i v e b l i n d n e s s , b i l a t e r a l c h e r r y r e d s p o t s , hyperacusis, hepatosplenomegaly and hypotonia, w i t h o n s e t of symptoms by 9 months of l i f e . Serum and WBC 0-D-N-acetylglucosaminidase a c t i v i t i e s were reduced t o l e v e l s l e s s than 1% normal. O b l i g a t e heterozygotes showed reduced l e v e l s of t o t a l serum hexosaminidase a c t i v i t y and lower than normal % B form: SERUM HEXOSAMINIDASE (nanomoles/hr/ml . )T o t a l % B form P a t i e n t 3 2 Mother 394 1 4 . 5 F a t h e r 382 12.7 C o n t r o l s 506-950 21-35 A s i m i l a r r e d u c t i o n of total. hexosaminidase t o 8% normal v a l u e s was found i n c u l t i v a t e d s k i n f i b r o b l a s t s from o u r pat i e n t . I n t e r e s t i n g l y , l e v e l s of hexosaminidase were r a i s e d up t o 25% normal v a l u e when f i b r o b l a s t s were grown i n n u t r it i o n a l medium supplemented w i t h prednisolone o r c o r t i s o n e ( 1 m l This o b s e r v a t i o n , i f confirmed i n o t h e r c a s e s of Sandhoff d i s e a s e might s u g g e s t a t h e r a p e u t i c approach i n t h i s r a p i d l y p r o g r e s s i v e ...