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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...
Mutations01:39

Mutations

Overview
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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).
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...

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Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells
08:18

Application of Laser Micro-irradiation for Examination of Single and Double Strand Break Repair in Mammalian Cells

Published on: September 5, 2017

Radiation-quality dependent cellular response in mutation induction in normal human cells.

Masao Suzuki1, Chizuru Tsuruoka, Yukio Uchihori

  • 1Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan. m_suzuki@nirs.go.jp

Journal of Radiation Research
|August 15, 2009
PubMed
Summary

Low-dose radiation pretreatment affects cell mutation frequency differently based on radiation type. Heavy ions like helium and carbon increased mutations, while neutrons decreased them, showing radiation quality dependence.

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Area of Science:

  • Radiation biology
  • Cellular and molecular biology
  • Radiobiology

Background:

  • Cellular responses to radiation are crucial for understanding radiation effects.
  • Low-dose radiation exposure can induce complex cellular responses, including mutations.
  • Different radiation types possess varying physical characteristics (e.g., linear energy transfer - LET) that can influence biological outcomes.

Purpose of the Study:

  • To investigate the impact of low-dose pretreatment with various radiation types on subsequent cellular responses, specifically cell killing and mutation induction.
  • To determine if the type of radiation used for pretreatment influences the mutation frequency induced by a challenging X-ray dose.
  • To elucidate the radiation-quality dependence of cellular responses following low-dose irradiation.

Main Methods:

  • Normal human fibroblasts were pretreated with low-dose irradiations of gamma rays, neutrons, helium ions, carbon ions, or iron ions.
  • Pretreated cells were subsequently exposed to a challenging X-ray dose (1.5 Gy).
  • Cell-killing effects were assessed using a colony formation assay.
  • Mutation induction was quantified by measuring 6-thioguanine resistant clones at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus.

Main Results:

  • No significant differences in cell-killing effects were observed across different radiation pretreatment types.
  • Pretreatment with gamma rays did not alter X-ray-induced mutation frequency compared to unpretreated cells.
  • Pretreatment with helium and carbon ions significantly increased X-ray-induced mutation frequency (1.8x and 4.0x, respectively).
  • Iron ion pretreatment resulted in mutation frequencies similar to unpretreated or gamma-ray pretreated cells.
  • Neutron pretreatment reduced X-ray-induced mutation frequency to 0.15 times that of unpretreated cells.

Conclusions:

  • Cellular responses, particularly mutation induction, following low-dose or low-fluence radiation pretreatment are dependent on the quality (type) of radiation.
  • High LET heavy ions like carbon and helium can sensitize cells to X-ray-induced mutations, while neutrons exhibit a protective effect.
  • These findings highlight the complex interplay between radiation quality and cellular radiosensitivity, with implications for radiation protection and therapy.