INHIBITION OF C-MYC EXPRESSION INDUCED BY 4-HYDROXYNONENAL, A PRODUCTOF LIPID-PEROXIDATION, IN THE HL-60 HUMAN LEUKEMIC-CELL LINE

4-Hydroxynonenal is a highly reactive aldehyde, produced by cellular l ipid peroxidation, able to inhibit cell proliferation ''in vitro'' and ''in vivo''. Its concentration in non proliferating cells ranges up t o 1 mu M, whereas in the highly undifferentiated tumour cells, it is v ery low or undetectable. We have now demonstrated that micromolar conc entrations of 4-hydroxynonenal inhibit c-myc but not N-ras expression in HL-60 human leukemic cells. This inhibitory effect is observed afte r an incubation of 1 hour with both 1 and 10 mu M aldehyde. Moreover, we report that down- regulation of c-myc expression increses when repe ated additions of 1 mu M 4-hydroxynonenal are performed, to maintain t he cells in presence of aldehyde for 7.5 hours. These results indicate that not only the concentration but also the length of exposure to th e aldehyde is important in determining the extent of the c-myc express ion inhibition and suggest a role of lipid peroxidation products in th e control of gene expressions. (C) 1994 Academic Press, Inc.