[Effect of arsenic on the incorporation of 14C-thymidine into DNAP of phytohaemagglutinin-treated lymphocytes (author's transl)].

Abstract

In lymphocyte cultures stimulated with PHA Na2HAsO4 is able, independent of the arsenic doses used (10 mug, 30 mug, 50 mug/ml culture medium), to increase the 14C-thymidine incorporation in acid precipitable biopolymers. The increase was 17 plus or minus 4% at 1 hr exposure to arsenic, compared with control cultures which were not exposed to arsenic. The administration of 30 mug and 50 mug Na2HAsO4/ml medium at incubation periods between 2 and 18 hrs resulted in a decrease in the radioactive incorporation rate into the DNA which was dependent on dose and time. Using 10 mug Na2HAsO4 per ml medium, the 1 hr stimulation is followed by an inhibition (up to approximately 35%, control equals 100%), which lasts for approximately 3 hrs. This is followed by an increase in the 14C-thymidine incorporation into the DNA for a further 2 hrs. The course of the inhibition curve with 10 mug Na2HAsO4 and with exposure times between 6 and 18 hrs the decreases again dependent on dose and time. As an explanation of the stimulation of the 14C-thymidine utilisation by arsenic, we suppose an increased repair activity. This may lead to a situation where (labelled) bases which are added outside the synthesis phase are incorporated into the DNA. The inhibition of 14C-thymidine incorporation which is dependent on dosage and time, with larger doses of arsenic can be explained by a prevailing influence of enzymes of the synthesis system (e.g. polymer arsenic), while the unusual course of the inhibition curve under the influence of 10 mug Na2HAsO4 shows that an activation and inhibition of enzyme systems (synthesis and repair) which is displaced in time is taking place. Apart from this, disturbances of regulation processes of the DNA replication and the initiation overlap can also be suspected as a cause of the phenomena observed.