Induction of incoordinate synthesis of muscle proteins by the tumor promoter TPA and the carcinogen EMS.

Abstract

Combined cytoimmunofluorescent, electron microscopic, and biochemical studies have repeatedly demonstrated the following about normal myogenesis: (1) That the switch in differentiation programs from replicating presumptive myoblasts to their daughter postmitotic myoblasts occurs prior to fusion; (2) That this switch requires DNA synthesis, but not cytokinesis; (3) That 6–12 hours after their last mitosis, both daughter definitive myoblasts initiate the coordinate synthesis of muscle-specific myosin heavy and light chains, tropomyosin, C-protein and M-band protein and at about this time become fusion competent. This switch in differentiation programs also involves the initiation of the synthesis of the muscle-specific intermediate filament protein, desmin; (4) That this sequence of events begins in chick myotomes at stages 14–15 and in chick limb buds at stages 20–21; (5) That there is a lag phase of hours between the earliest detection of these muscle-specific isoforms in mononucleated postmitotic myoblasts and their assembly into myofibrils. During this lag period, myofibrillar proteins and desmin appear to be widely distributed throughout the sarcoplasm.