Xenobiotics induce liver adaptive responses which involve increases of enzymes, increases of cell organelles and organ growth. These processes presumably represent increased functional capacity. The induction of adaptive liver growth by the xenobiotic mirex will be studied in the laboratory rat. Mirex-induced liver growth is a dramtic response, in that there is an 80% increase in liver mass in 72 hours following a single oral dose (100 mg/kg body weight). This response has a hyperplastic and a hypertrophic component. Although the adaptive liver growth response is an expression of both components, it is possible to experimentally separate the two components into discrete responses and to study each independently of the other. The hypertrophic component of mirex-induced adaptive liver growth is corticosterone dependent. The hyperplastic component is corticosterone independent, but appears to be dependent on other biochemical secretions from the adrenal gland. The hypertrophic response can be induced in adrenalectomized animals dosed with mirex and supplemented with corticosterone. The hyperplastic response can be induced in adrenalectomized animals dosed with mirex. Using this model system, the biochemical events which occur in hyperplasia and hypertrophy will be studied. The role of adrenal hormones in mediating adaptive liver growth will be investigated. The sequence of events in the inductive growth process will be established. The results of these studies will provide a clearer understanding of the factors which control organ and/or cell size.
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