Abstract: Inorganic arsenic has been shown as an environmental carcinogen, exposure to arsenic can resulted in high incidence of multiple diseases including cancer. Paradoxically, several arsenic compounds such as arsenic trioxide have been used effectively to treat promyelocytic leukaemia and other solid tumors. It has been shown that the tumor suppressor p53 plays important roles in cancer therapy. However, the roles of p53 on the treatment effects of ATO are still uncertain. The nematode Caenorhabditis elegans has been shown as a good model for studying the regulative effects of p53 on DNA damage and cell cycle because it has only a single p53-like gene cep-1. In the present study, the therapeutic effects of ATO on the gonad tumorous growth were studied using gld-1(q485) mutated worms. The results presented here indicated that ATO treatment extended the lifespan of gld-1(q485) mutants and inhibited tumorous growth of the gonad. ATO treatment induced cell cycle arrest in a dose- and time-dependent manner. It was also found that ATO treatment resulted in germline apoptosis in worms of N2 and gld-1(q485) mutants. By using worm strains carrying mutated cep-1 alleles plus RNAi double gene knockout, it was found that ATO exerted its antitumor activity on gld-1(q485) mutants through the induction of cell cycle arrest in a CEP-1/p53-independent manner and germline apoptosis in a CEP-1/p53-dependent manner.

Key words: arsenic trioxide, Caenorhabditis elegans, CEP-1/p53, cell cycle arrest, apoptosis