High Melanin Content in Melanoma Cells Contributes to Enhanced DNA Damage after Rose Bengal Photosensitization

Paloma Kalegari1, Daniela Morais Leme2, Geonildo Rodrigo Disner2

  • 1Departamento de Bioquímica e Biologia Molecular, Programa de Pós-graduação em Ciências (Bioquímica), Setor de Ciências Biológicas, UFPR, Curitiba, Brazil.

Insights

High melanin content in melanoma cells may worsen DNA damage after Rose Bengal acetate-photodynamic therapy (RBAc-PDT). This sustained oxidative stress increases specific DNA lesions, impacting treatment outcomes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Dermatology

Background:

  • Melanoma arises from melanocytes.
  • UVA and visible light irradiation of melanin generates reactive oxygen species (ROS), including singlet molecular oxygen (1 O2).

Purpose of the Study:

  • To investigate DNA damage in melanoma cells (B16-F10) with varying melanin levels upon 1 O2 generation.
  • To assess the impact of Rose Bengal acetate-photodynamic therapy (RBAc-PDT) on DNA lesions.

Main Methods:

  • Utilized Rose Bengal acetate (RBAc) and 526 nm visible light for RBAc-PDT.
  • Employed a modified comet assay with hOGG1 and T4 endonuclease V to detect specific DNA lesions (8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers).
  • Measured ROS levels and antioxidant enzyme activity to confirm oxidative stress.

Main Results:

  • Light exposure (with or without RBAc) increased hOGG1- and T4endoV-sensitive DNA lesions.
  • hOGG1-sensitive lesions increased 18 hours post-irradiation, correlating with higher melanin content and sustained oxidative stress.
  • T4endoV-sensitive lesions decreased over the 18-hour period.

Conclusions:

  • Melanin content influences DNA damage levels in melanoma cells during RBAc-PDT.
  • Sustained oxidative stress, exacerbated by high melanin, contributes to specific DNA lesion formation post-irradiation.
  • Findings suggest melanin's role in modulating DNA damage response to photodynamic therapy in melanoma.

Related Concept Videos

Pigmentation01:19

Pigmentation

The color of the skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred to the keratinocytes via melanosomes.
Melanin occurs in two primary forms: eumelanin that provides black and brown pigment and pheomelanin that provides red color. Dark-skinned individuals produce more melanin than those with pale...
3.1K
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...
40.7K
Skin Cancer01:30

Skin Cancer

Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
4.8K
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...
3.9K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.7K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.4K