Caffeine release of radiation induced S and G2 phase arrest in V79 hamster cells: increase of histone messenger RNA levels and p34cdc2 activation.

The serine/threonine protein kinase p34cdc2 activity in V79 hamster cells 4 h after treatment with 7-Gy X-rays is similar to that of unirradiated cells. Nevertheless, the irradiated cells are arrested in the S and G2 phases of the cell cycle. The mRNA concentrations of histones H1 and H4 are reduced by a factor of about 2 in irradiated cells compared to unirradiated cells, as opposed to the mRNAs of high-mobility group I(Y) and 17 proteins which appear unchanged. Both the p34cdc2 activity and the mRNA concentrations of the histones rise within 30 min after the release of the radiation induced cell cycle block by caffeine. During this time span the p34cdc2 activity increases about 4-fold and the histone mRNA levels recover approximately to those of an exponentially growing cell population. Regulatory pathways influenced in irradiated and in subsequently caffeine treated cells apparently interact with basic cell cycle control mechanisms.