CHEMICAL MUTAGENIC AGENTS

Shirin Shahana.N
BSc.Biotechnology
SIAS

1. C H E M I C A L M U T A G E N I C AGE N T S S h i r i n S h a h a n a . N B S c . B i o t e c h n o l o g y S I A S

2. CHEMICA L M U T A G E N S A mutage n i s a n y s u b s t a n c e o r a g e n t t h a t c a n c a u s e a m u t a t i o n , o r c h a n g e i n t h e s e q u e n c e o r structu r e o f D N A . C h e m i c a l s a r e a c t u a l l y d a n g e r o u s f o r t h e e n t i r e w o r l d . T h e f i r s t m u t a g e n i c e f f e c t o f t h e n i t r o g e n m u s t a r d w a s r e p o r t e d b y C h a r l o t t e A u r e b a c h i n 1 9 4 2 . Ni t r o g e n m u s t a r d i s a g a s u s e d d u r i n g W o r l d w a r 1 a n d 2 .

3. 1 ) B A S E ANALOG S The s e a r e c h e m i c a l s s i m i l a r t o t h e b a s e s o f D N A p u r i n e a n d p y r i m i d i n e s o r s t r u c t u r a l l y re s e m b l e t h e D N A b a s e s . B r o m o u r a c i l a n d A m i n o p u r i n e a r e 2 c o m m o n b a s e a n a l o g s i n c o r p o r a t e d int o D N A i n s t e a d o f n o r m a l b a s e s , d u r u n g t h e p r o c e s s o f r e p l i c a t i o n . T h e 5 - b r o m o u r a c i l a r e a r t i f i c i a l l y synthe s i z e d m o l e c u l e s - a b a s e a n a l o g u t i l i z e d i n t h e genet i c resea r c h w h i c h i s i n c o r p o r a t e d i n D N A i n p l a c e o f t h e t h y m i n e .

4. Instead of the methyl group of the thymine,in the bromo uracil contains Bromine group-highly resemble to the thymine. I t pair s with the adenine as like the t h y m i n e and produces the mutation .

5. M e c h a n i s m o f 5 - bromouraci l a c t i o n i s q u i t e i n t e r e s t i n g . During replication, instead of thymine, it generates guanine which pairs with the cytosine .

6. T h u s , t h e T A basepa i r i s r e p l a c e d b y G C b a s e p a i r at t h e e n d o f t h e repli c a t i o n a n d t h i s happen s b e c a u s e o f t h e t a u t o m e r i c s h i f t o f 5 - B U f r o m ' e n o l ' t o ' k e t o ' f o r m . T h e e n t i r e m e c h a n i s m i s s h o w n b e l o w : -

7. Aminopuri n e s Another base analogue is amino purine which is similar to the a d e n i n e and can pair with either T o r C , a l t h o u g h p a i r i n g w i t h C i s less frequent. It can also cause A T - GC or GC - A T transition during the replication.

8. 2 ) A L K Y L A T I N G A G E N T S Ethylni t r o s o u r e a , mus t a r d gas a n d v i n y l c h l o r i d e a r e c o m m o n a l k y l a t i n g a g e n t s t h a t a d d a l k y l g r o u p t o t h e D N A a n d d a m a g e s i t . T h e a g e n t s i n d u c e base - p a i r i n g e r r o r s b y i n c r e a s i n g i o n i z a t i o n a n d p r o d u c e s gap s i n the D N A st r a n d . T h e a l k y l a t e d p u r i n e b a s e s a r e r e m o v e d b y t h e p h e n o m e n o n c a l l e d depurination , a l t h o u g h d e p u r i n a t i o n i s n o t m u t a g e n i c a n d c a n b e r e p a i r e d b y t h e D N A - r e p a i r pathw a y .

9. C o m m o n A l k y l a t i n g A g e n t s Methylhydrazine . T e m o z o l o m i d e D a c a r b a z i n e B u s u l f a n I o m u s t i n " W h e n n i t r i t e s a r e a d d e d t o s m o k e d m e a t , i t f o r m s n i t r o s a m i n e l i k e m u t a g e n t h a t c a n b r e a k D N A o r c r e a t e s D N A c r o s s l i n k i n g .

10. 3 ) I N T E R C A L A T I N G A G E N T S E t B r - E t h i d i u m B r o m i d e i s a n e x a m p l e . Othe r i n t e r c a l a t i n g a g e n t s l i k e p r o f l a v i n , acridine ora n g e o p e r a t e d by t h e s a m e m e c h a n i s m a l i k e t h e E t B r . T h e m o l e c u l e s i n t e r c a l a t e b e t w e e n t h e b a s e s o f D N A a n d d i s r u p t i t s s t r u c t u r e . I f i t i s i n c o r p o r a t e d d u r i n g t h e r e p l i c a t i o n , i t c a n c a u s e f r a m e s h i f t m u t a t i o n a n d a l s o b l o c k s t r a n s c r i p t i o n .

11. • I n t e r c a l a t i n g a g e n t s e i t h e r c a u s e i n s e r t i o n o r d e l e t i o n a n d d i s r u p t s t h e D N A s t r u c t u r e .

12. 4 ) M E T A L I O N S N i c k e l , c h r o m i u m , c o b a l t , c a d m i u m , arsen i c , iro n a r e s o m e example s . T h e m e t a l i o n w o r k b y p r i d u c i n g R O S ( r e a c t i v e o x y g e n s p e c i e s ) h i n d e r i n g t h e D N A r e p a i r p a t h w a y , c a u s e D N A h y p e r m e t h y l a t i o n o r m a y d i r e c t l y d a m a g e s t h e D N A .

13. OT H E R C H E M I C A L M U T A G E N S ROS , b e n z e n e , s y n t h e t u c r u b b e r a n d r u b b e r p l a s t i c s , s o d i u m a z i d e , a r o m a t i c amines , a l k a l o i d s , deam i n a t i n g agents a n d PAH ( p o l y c y c l i c a r o m a t i c hydr o c a r b o n s ) a r e o t h e r m u t a g e n s t h a t c r e a t e d i f f e r e n t mutation s .

14. T H A N K Y O U . . .