The common assumption that the seed failure in interploidy crosses of flowering plants is due to parental genomic imprinting is based on vague interpretations and needs reevaluation since the general question is involved, how differentiation is timed so that cell progenies, while specializing, pass through proper numbers of amplification divisions before proliferation ceases. As recently confirmed, endosperm differentiation is accelerated or de-accelerated, depending upon whether polyploid females are crossed with diploid males, or vice-versa. Unlike the zygote, the first cell of the endosperm is determined to produce a tissue that successively induces growth of maternal tissues, stimulates and nourishes the embryo, and finally ceases cell cycling. Altered timing of endosperm differentiation, thus, perturbs seed development. During fertilization, only the female genomes contribute cytoplasmic equivalents to endosperm development so that in interploidy crosses, the initial amount of cytoplasm per chromosome set is altered, and due to semi-autonomy of cytoplasmic growth, altered numbers of division cycles are needed to provide the amount of cytoplasmic organelles required for differentiation. Cytoplasmic semi-autonomy and dependence of differentiation on an increase in cytoplasm has been shown in other tissues of plants and animals, thus, revealing a common mechanism for intracellular timing of differentiation. As demonstrated, imprinted genes can alter the extent of cell proliferation by interfering with this mechanism.

It has been suggested that cancer ought to be regarded as a disease of cell differentiation. In multicellular organisms, indeed, the control of cell multiplication is linked to cell specialization: During the process of differentiation embryonic cells, while cycling, acquire the ability to perform specialized functions. This ability is incompatible with cell cycling which, as a consequence, is repressed with forthcoming differentiation. Thus, the number of amplification divisions that occur during the period while differentiation is proceeding decides on the number of specialized cells produced. The progress in differentiation, contrary to usual assumptions, is accompanied by an increase in the cellular content of cytoplasm. The reason must be that cell specialization requires a specific amount and array of membrane-bounded cytoplasmic structures. Since the multiplication of these structures depends on membranous templates, their amount increases only if more cytoplasm is produced per cycle than required for a doubling, thus constituting an intracellular timer of differentiation: The larger the net rate of cytoplasmic growth per cell cycle, the fewer cycles occur. Extracellular signals modulate cell multiplication by altering the net rate of cytoplasmic growth. Each persisting alteration, however, that reduces this rate to zero, prevents differentiation, and thus causes the cells to retain embryonic capabilities and to initiate cancer. Cancer cells can be induced to differentiate and cease proliferation by support of cytoplasmic growth. This corroborates the suggestion that cancer must be regarded as a disease of cell differentiation and our conclusion that cancer is caused by a deficiency in cytoplasmic growth. Support of the latter must be an efficient principle in cancer therapy although limited by the organism's dependence on cell renewal.

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In several systems a paradoxical reduction of radiation damage with increasing dose, termed reversion, has been observed. In the fern Osmunda regalis the percentage of cells which does not die but stays alive, although reproductively sterile, increases with dose. The assumed mechanism of this effect is a continuation of cytoplasmic growth during radiation-induced mitotic delay which induces terminal differentiation (early differentiation) thus preventing mitosis and the expression of chromosomal injury. Suppression of cytoplasmic growth after irradiation should abrogate reversion. This was tested using anoxia. Reversion was suppressed by storage of the sporelings in nitrogen for 8 h or more after X-rays, but was not suppressed by storage in 0.27 microM oxygen nor by a 60-min exposure to air after irradiation and before storage in nitrogen. Anoxia before irradiation in air had no effect. Anoxia only during irradiation showed an OER of about 2 for the reversion peak. The partial abrogation of reversion is consistent with the assumed mechanism. Marked reversion also was observed after 14.7 MeV neutrons.