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The Effects of Actinomycin D and Methylcholanthrene on the Cytology and RNA and Protein Synthesis in Prostatic Epithelium Grown in Vitro

Strangeways Research Laboratory, Cambridge, England

The effects of actinomycin D and methylcholanthrene on the cytology of the rat ventral prostate gland grown in vitro have been studied and correlated with changes in RNA and protein synthesis. Prostatic explants were exposed for 2 days to actinomycin D at concentrations of 0.15 and 0.5 µg/ml medium or to a combination of 0.15 µg/ml actinomycin and 4 µg/ml of methylcholanthrene and transferred for 4 or 7 days to control medium or medium containing methylcholanthrene.

A dose of 0.5 µg actinomycin D causes irreversible breakdown of the prostatic epithelium. After a dose of 0.15 µg/ml, the damage is much less marked and is followed by complete recovery and hyperplasia of the prostatic epithelium.

RNA synthesis, determined autoradiographically by uridine-5-³H incorporation, is severely suppressed by 0.15 µg/ml of actinomycin, but it recovers after 4 days and rises to three times the control level after withdrawal of the antibiotic. Protein synthesis, measured by the incorporation of leucine-4,5-³H, is only slightly inhibited by the antibiotic. The difference between the low uridine and high leucine incorporation suggests the existence of long-lived messenger RNA in the prostatic epithelium.

Methylcholanthrene alone induces epithelial hyperplasia which is associated with a gradual increase of uridine incorporation and a transient stimulation of leucine incorporation. Combining methylcholanthrene with actinomycin prevents the cellular damage produced by actinomycin alone, allows cell multiplication to proceed, and partially inhibits the suppression of uridine incorporation by the antibiotic. After transfer to medium containing methylcholanthrene but no antibiotic, the hyperplasia is accelerated and increased as compared with that seen after continuous treatment with methylcholanthrene alone. The interaction between methylcholanthrene and actinomycin D is discussed in the context of possible hydrocarbon binding sites in the cell nucleus.

Received 7/11/68. Accepted 9/20/68.