Advances in Clinical Toxicology (ACT)

ISSN: 2577-4328

Research Article

How Bulky of Base Adducts can be Responsible for Clastogenicity rather than Mutagenicity?

Authors: Kikuchi Y, Galbreath HE, Kobayashi R, Kudou S, Matsumoto K, Hasegawa A, Saito T, Sato K, Honma T, Yamamoto A, Arai H, Kadoma Y, Kawaguchi S, Furuya K, Kobune M, Nakamura T and Yu F Sasaki*

DOI: 10.23880/act-16000256

Abstract

Two types of TK mutants are induced by genotoxic factors; normally growing (NG) TK mutants due to point mutations of targeted TK locus, and slowly growing (SG) mutants due to gross structural changes involving the growth-regulating gene outside targeted TK locus. In this study, human lymphoblstoid WTK1 cells were used to consider how bulky n- alkylated bases can induce SG mutants. For this purpose, n-alkyl methanesulfonates (AMS) having an n-alkyl group with 3-7 carbons [n-propy methanesulfonate (PMS), n-butyl methanesulfonate (BMS), n-pentyl methanesulfonate (PeMS), n- hexyl methanesulfonate (HexMS), and heptyl methanesulfonate(HepMS)] were synthesized. n-alkyl methanesulfonates having n-alkyl groups with 1-7 carbons induced NG mutants, but n-alkyl methanesulfonates having n-alkyl groups with ≥4 carbons but not with ≤3 carbons induced SG mutants. n-Alkyl methanesulfonates having n-Alkyl groups with ≥4 carbons have been shown to induce bulky adducts that cause disturbances to the helical DNA structure and are removed by nucleotide excision repair. It could be considered that n-alkyl groups with ≥4 carbons causing disturbances to the helical DNA structure induce SG mutants to result in clastogenicity rather than mutagenicity.

Keywords: Bulky adducts; n-Alkyl methanesulfonates; Slowly growing TK mutant; Normally growing TK mutants; Clastogenicity; Mutagenicity

View PDF

F1 europub scilit.net

Chat with us on WhatsApp

Welcome to Medwin Publishers. How can we help you today?