"Hit and run" transformation leading to carcinogenesis

J K McDougall1

  • 1Fred Hutchinson Cancer Research Center at Seattle, WA 98109, USA.

Insights

Herpesvirus DNA fragments can cause cells to become cancerous, even without lasting DNA presence. This "hit-and-run" transformation, observed in rodent cells, suggests a mutagenic mechanism for viral oncogenesis.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • Subgenomic DNA fragments from herpes simplex virus (HSV) and cytomegalovirus (CMV) have demonstrated the ability to induce neoplastic transformation in rodent cells in vitro.
  • The transfected viral DNA is not permanently integrated into the host genome of transformed cells, and viral proteins are transiently expressed and undetectable in established cell lines.

Purpose of the Study:

  • To investigate the phenomenon of 'hit-and-run' transformation induced by herpesvirus DNA fragments.
  • To explore the potential mutagenic properties of viral DNA fragments in cellular transformation.
  • To assess the applicability of these findings to human cells, beyond observations in rodent models.

Main Methods:

  • In vitro transfection of rodent cells with subgenomic fragments of HSV and CMV.
  • Analysis of DNA persistence and viral protein expression in transformed cell lines.
  • Evaluation of mutagenic potential of the transfected DNA fragments.

Main Results:

  • Transfected viral DNA fragments did not persist long-term in neoplastic rodent cells.
  • Viral proteins were transiently expressed and not detectable in established transformed cell lines.
  • Evidence suggests that the transforming DNA fragments possess mutagenic properties.

Conclusions:

  • The 'hit-and-run' transformation model provides a plausible explanation for neoplastic transformation induced by HSV and CMV DNA in vitro.
  • This mechanism, involving transient DNA presence and mutagenic effects, has been observed consistently across multiple laboratories for over two decades.
  • Further research is needed to confirm if these effects extend to human cells.

Related Concept Videos

Mutations01:39

Mutations

Overview
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
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...
Bioactivation and Tissue Toxicity01:25

Bioactivation and Tissue Toxicity

Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
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).