Evidence for an Aneugenic Mechanism of Action for Micronucleus Induction by Black Cohosh Extract

D.T. Bernacki1, S.M. Bryce1, J.C. Bemis1, S.D. Dertinger1, K.L. Witt2, S.L. Smith-Roe2

1 Litron Laboratories
2 Division of the National Toxicology Program, NIEHS

Environmental and Molecular Mutagenesis
Volume 60, Issue 9, 01 December 2019, Pages 845-856

Black cohosh and black cohosh extracts (BCE) are popular botanical products that are routinely used to address gynecological ailments. Due to public concern about the safety of a number of botanical supplements, the National Toxicology Program (NTP) decided to evaluate black cohosh and its extracts, among others. Since black cohosh extract is one of the top ten selling botanical supplements in the United States, a deeper understanding of its toxicological properties and mechanism-of-action were of interest to researchers at NIEHS/NTP and Litron.
Based on previous in vivo studies carried out by NTP and Integrated Laboratory Systems (ILS), BCEs were shown to induce micronuclei formation when studied using Litron’s in vivo MicroFlow micronucleus kit. In the current study, in vitro micronucleus formation also increased significantly in human lymphoblastoid TK6 cells when studied using Litron’s in vitro MicroFlow micronucleus kit.
To further elucidate a mechanism-of-action, NTP decided to use Litron’s in vitro MultiFlow DNA Damage Kit and Litron’s MultiFlow Aneugen Molecular Mechanism Kit to gather this information. Based on the use of the MultiFlow kits, it was determined that BCEs are destabilizing microtubules in vitro, and this is leading to an aneugenic mode-of-action for these complex mixtures.