The effect of parahydroxylation of diphenylhydantoin on metaphase accumulation.

DPH has a colchicine-like action on metaphase arrest of cultured human lymphocytes. The first step in detoxification of DPH increased its power to accumulate metaphases 3-fold. This hydroxy derivative [5-[4-hydroxyphenyl]-5-phenylhydantoin, HPPH] 3.6 X 10(-4) M was equivalent colchicine 1 x 10(-5) M in its power to inhibit metaphase completion. The effect of HPPH on mitosis was reversible; colchicine effect was not reversed and vincristine effect was partially reversed by washing drug from the medium. Hydroxylation of DPH did not change its inhibition of DNA synthesis and enhanced inhibition of protein synthesis to a minor degree. Detoxification increased the colchicine-like action of DPH.