Related Experiment Video

Updated: Aug 7, 2026

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
08:04

Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro

Published on: March 18, 2014

Arsenite induces delayed mutagenesis and transformation in human osteosarcoma cells at extremely low concentrations

Kanae Mure1, Ahmed N Uddin, Laura C Lopez

  • 1New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, New York 10987, USA.

Environmental and Molecular Mutagenesis
|June 13, 2003
PubMed

Insights

Long-term exposure to low concentrations of arsenite causes delayed mutagenesis and cell transformation. Arsenite itself, not its metabolites, drives these effects, suggesting progressive genomic instability.

Area of Science:

  • Environmental Health
  • Toxicology
  • Carcinogenesis

Background:

  • Arsenite is a known human carcinogen, but its precise mechanism of action remains unclear.
  • Previous research indicated arsenite transforms human osteosarcoma cells (HOS) to anchorage-independence after prolonged exposure (8 weeks).

Purpose of the Study:

  • To investigate the mutagenic and transformative effects of chronic, low-dose arsenite exposure.
  • To determine if arsenite metabolites contribute to its carcinogenic effects.

Main Methods:

  • Utilized a spontaneous mutagenesis assay with chronic exposure of HOS cells to arsenite.
  • Assessed mutagenesis and transformation rates over multiple cell generations.
  • Investigated the role of monomethylarsonous acid (MMA(III)), a potential arsenite metabolite.

Main Results:

  • Arsenite induced a delayed, dose-dependent increase in mutagenesis after approximately 20 generations.
  • Cell transformation required over 30 generations of continuous arsenite exposure.
  • Arsenite, not MMA(III), was responsible for the observed delayed mutagenesis and transformation, and induced dose-dependent dihydrofolate reductase (DHFR) gene amplification.

Conclusions:

  • Long-term, low-level arsenite exposure can lead to delayed mutagenesis and transformation.
  • Arsenite itself, rather than its metabolites, appears to be the primary driver of these effects.
  • These findings suggest arsenite may promote progressive genomic instability through signaling pathway alterations.

More Related Videos

In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration09:24

In Vitro Scratch Assay to Demonstrate Effects of Arsenic on Skin Cell Migration

Published on: February 23, 2019

Lethality Bioassay Using Artemia salina L.09:09

Lethality Bioassay Using Artemia salina L.

Published on: October 11, 2022

Related Concept Videos

Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
Spontaneous and Induced Mutations01:30

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).