Analysis of historical negative control group data from the in vitro micronucleus assay using human lymphocytes
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
Authors: Lovell, David P.; Fellow, Mick; Elhajouji, Azeddine; Farabaugh, Christopher S.; Gilby, Ben G.; Hashimoto, Kiyohiro; Li, Yan; Roy, Shambhu; Schuler, Maik; Whitwell, James; Tanir, Jennifer Y.
Abstract
A database of the micronuclei counts was built up for historical negative control data from human lymphocyte in vitro micronuclei tests (MnVit) carried out in 8 laboratories with experience of the method. The mean incidence of micronucleated cells (mnt)/1000 cells ranged from 2.2/1000 to 15.9/1000. There were no large differences in incidence between the presence or absence of S9 mix or between different treatment lengths. There was also little evidence that different solvents affected the numbers of micronuclei appreciably. A number of laboratories did show significant inter-experiment variability, indicating that there remained unidentified factors affecting frequencies. Donor variance may be one such factor. Inter-individual variability may explain some of these differences. The approximate 7.5-fold difference in mnt/1000 scores in a relatively small group of experienced laboratories illustrates the potential complications that can arise if a metric like a fold increase was considered the only biologically important finding. Although there is inherent variability between experiments, it was evident that within a laboratory the overall laboratory mean remains constant over time. It is believed that these findings will provide help to laboratories conducting studies using human lymphocytes in the MnVit and to those involved in the assessment of MnVit results.
Biodistribution of Modular Nanotransporter Carrying Auger Electron Emitter and Targeted at Melanoma Cells in Murine Tumor Model
PHYSICS OF CANCER: INTERDISCIPLINARY PROBLEMS AND CLINICAL APPLICATIONS (PC IPCA)
Authors: Vorontsova, M. S.; Morozova, N. B.; Karmakova, T. A.; Rosenkranz, A. A.; Slastnikova, T. A.; Petriev, V. M.; Smoryzanova, O. A.; Tischenko, V. K.; Yakubovskaya, R. I.; Kaprin, A. D.; Sobolev, A. S.
Abstract
Recombinant modular nanotransporter containing alpha-melanocyte-stimulating hormone peptide sequence (MNT-MSH) as a ligand module was designed for nucleus-targeted delivery of cytotoxic agents into melanoma cells. MNT-MSH radiolabeled with Auger electron emitter (In-111-NOTA-MNT-MSH) showed a high antitumor efficacy in mice bearing syngeneic melanoma after intratumoral (i.t.) injection. This study is aimed at evaluating the biodistribution of the radioconjugate in melanoma tumor model in vivo. In-111-NOTA-MNT-MSH was administered i.t. in C57Bl/6j mice bearing subcutaneously implanted B16-F1 murine melanoma cells, expressing high levels of MCR1. The tissue uptake of radioactivity was determined ex vivo by gamma-counter measurements. The intravenous route of administration did not provide a desirable level of radioactivity accumulation in the tumor, possibly, due to a high uptake of the transporter in liver tissue. After i.t. administration In-111-NOTA-MNT-MSH provided a high local retention of radionuclide, ranged from 400 to 350 % ID/g within at least 48 hours post-injection. MNT containing Auger electron emitter and alpha-MSH peptide as vector ligand could be a promising basis for radiopharmaceutical preparations intended for melanoma treatment.