Cultured peripheral lymphocytes: one biologic indicator of potential drug hazard

Abstract

Peripheral human lymphocytes (Pis) of three categories of patients under therapy with four drugs: niridazolc and tartar emetic for schistosomiasis, diphenylhydantoin for grand mal epilepsy and isoniazid for pulmonary and abdominal tuberculosis were cultured in-vitro with and without photodamageglutenin (PHA) stimulation. The four drugs revealed a significant incidence of variable degrees of nucleonchromosomal pathology under the effect of PHA. Micronuclei. nuclear fragmentation and reduced Pis mitotic response to PHA were specifically notable with tartar emetic. Multinucleation, polyploidy and different grades of chromosome fragility were more conspicuous with niridazole and diphenylhydantoin and to a lesser degree with isoniazid. Niridazole was the only drug that effected histo - genesis and binucleation of Piz in absence of PHA and induced high incidence of giant polynucleated cells on stimulation with PHA. Those niridazole induced effects arc reported for the first time. In view of the hazards of such in-vitro nucleus chromosomal findings which might serve as biologic indicators of an oncogenic, teratogenic or mutagenic potential of those drugs, any extrapolation as to their in-vivo significance should be critically evaluated. The list of environmental agents physical, chemical and biologic which are known to break chromosomes is steadily growing. Evidence is accumulating that some of those agents may be oncogenic, others may well be mutagenic or teratogenic. Genetic diseases known to manifest early somatic cell chromosome breakage of some tissues are prone to develop cancer in the same tissues e.g. ataxia telangiectasia, Fanconi's anemias. Bloom's syndrome and xeroderma pigmentosum. Hence as the number of pharmaceutical drugs and chemicals which are ingested by man or which pollute his environment increases, biologic safety against an anticipated increase in the incidence of breakage of somatic and may be germinal cells chromosomes should be ensured. The present study was undertaken to determine any in-vitro detectable effect on cultured peripheral lymphocytes, of some drugs used for therapy of three highly prevalent diseases namely: schistosomiasis, tuberculosis and epilepsy