In vitro induction of segregational errors of chromosomes by natural cannabinoids in normal human lymphocytes

It has been shown that segregational errors (SE) of chromosomes can be induced by olivetol and several halogenated inhalation anesthetics. The purpose of this study was to examine the effects of natural cannabinoids - including delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) - on chromosome segregation. Lymphocytes obtained from healthy adult males were incubated with various concentrations of natural cannabinoids for 72 hours. Anaphase preparations were made from these cultures. A statistically significant increase in the incidence of SE of chromosomes was observed in the lymphocytes exposed to THC at a concentration of 3.2 x 10(-6) M, but not to CBN or CBD. A greater incidence of bridge formations, anaphase lags, micronuclei, and unequal segregations in bipolar divisions and multipolar divisions were observed in THC-treated lymphocytes, compared with the controls. However, only anaphase lags and unequal segregations in bipolar divisions reached statistically significant levels. It appears that THC affects the formation of microtubules and spindles and may be considered as a mitotic poison. The value of examining SE as a part of cytogenetic studies on chemical mutagens is emphasized. A description of a classification system of SE developed in our laboratory is also presented. This system can be applied to studies using both normal human lymphocyte cultures and lymphoid cell lines.