Because DON-induced apoptosis involves activation of PKR, Hck, and MAPKs (Zhou et al., 2003b; Zhou et al., 2005b) , the role of these kinases in rRNA cleavage was determined using selective inhibitors. Both the PKR inhibitor C-16 (0.1 and 0.3 lM) (Fig. 6A ) and the Hck inhibitor PP1 (5 and 25 lM) (Fig. 6B) were found to concentration dependently suppress DON-induced rRNA cleavage. Although the p38 inhibitor (SB 203580; 1 and 5 lM) also inhibited DON-induced rRNA cleavage concentration dependently (Fig. 6C) , inhibitors of JNK (SP600125; 0.2, 1, and 5 lM) and ERK (PO 98059; 20 and 100 lM) did not (data not shown) have suppressive effects. Thus, as has been observed for DONinduced apoptosis, PKR, Hck, and p38 appeared to be key upstream elements for DON-induced rRNA cleavage. 