Worm Breeder's Gazette 11(5): 100

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Effects of Okadaic Acid and Mezerein on C. elegans

Ken-ichiro Higashi and Johji Miwa

The tumor promoting phorbol ester TPA causes severe perturbation in 
the behavior and growth of C.  elegans.  We analyzed TPA-resistant 
mutants and found that all of the mutations located on the tpa-1 gene, 
which codes a protein kinase C homologue.
To investigate in more detail how tumor promoters act in behavior 
and development of C.  elegans, we have studied other types of tumor 
promoters.  One is okadaic acid, which inhibits protein phosphatase 1 
and 2A, and the other is mezerein, which, like TPA, activates protein 
kinase C, but is not a phorbol derivative.
1 M okadaic acid caused behavioral abnormality in L1 larvae (N2) and 
completely blocked the growth.  Although in L3 to adult worms behavior 
seems not to be affected, brood size greatly decreased and they died 
in a few days.
Mezerein was stronger than TPA in inducing behavioral change and 
developmental arrest in C.  elegans.  1 M mezerein strongly disturbed 
the worm behavior of L1 to adult.  The growth was completely blocked 
in all stages and the brood size was nearly zero even in the case of 
young adults.  Almost all treated worms died in a few days.
We have been trying to isolate mutants resistant to these substances.
So far, we have isolated 5 okadaic acid-resistant candidates and 2 
mezerein-resistant mutants from EMS mutagenized N2.  Their 
characterization and linkage mapping is now underway.  Interestingly, 
one of the mezerein-resistant mutants maps to linkage group IV (
probably tpa-1) but the other seemingly does not.  This may suggest 
the existence of a new gene which acts especially on mezerein, 
although mezerein is believed to act the same as TPA.  We plan to 
isolate additional mutants and characterize their gene products to 
understand their relationship to tpa-1.