B3 vitamin component fights carcinogen action in human cells, says research

October 24, 2017, FAPESP

Benzo[a]pyrene is a potent carcinogen and mutagen present in cigarette smoke, automotive exhaust, burnt wood fumes, barbecued and smoked meat etc.

Understanding the mechanisms whereby benzo[a]pyrene, which belongs to the class of (PAHs), may induce malignant transformation of human is the aim of a research project led by Ana Paula de Melo Loureiro, a professor at the University of São Paulo's School of Pharmaceutical Sciences (FCF-USP) in Brazil.

According to Loureiro, the idea is to identify the cellular pathways or sequences of biological reactions involved in the development of cancer and hence find possible targets for prevention or treatment of the disease. "Tests have shown that supplementing with nicotinamide riboside, one of the components of vitamin B3, protects cells and prevents ," she said. "We now want to find out exactly how this happens and whether the compound in question can be used in chemoprevention."

In experiments performed with regular lung cell cultures—more precisely, those of bronchial epithelial cells—were exposed to 0.5 and 1 micromolar (μM) benzo[a]pyrene for seven days. Recent data in the scientific literature suggests that the appearance of tumors is closely associated with genetic alterations and also with epigenetic alterations that may activate the expression of protumoral genes or silence protective genes, for example.

What most drew the scientists' attention, however, was a significant drop in the levels of metabolites involved in the production of energy for cells shortly after the first hour of exposure to benzo[a]pyrene. Throughout the exposure period, the cells readapted metabolically, and by the end of the period, the levels of metabolites had risen in exposed cells compared with the control group.

"It was for this reason that we had the idea of supplementing the cultures with nicotinamide riboside, a precursor to nicotinamide adenine dinucleotide [NAD+], which is essential to cellular metabolism and to the production of ATP [adenosine triphosphate, a molecule that stores energy for cell use]," Loureiro said.

Supplementation with nicotinamide riboside (1 μM) began 24 hours before exposure to benzo[a]pyrene and continued daily. Because benzo[a]pyrene is absorbed rapidly and biotransformed, it has to be replenished in the cell cultures every day, Loureiro explained.

At the end of the seven-day period, the cells were transferred to a semi-solid medium containing agarose, a polysaccharide obtained from algae, in order to prevent adhesion to the culture dish. The researcher says that a normal epithelial cell is unable to grow in this semi-solid medium without anchorage. "To make this possible, the expression of a number of genes and proteins must be altered so as to favor tumor development, for example by silencing the expression of cadherins [calcium-dependent adhesion molecules that form junctions to bind nearby cells together]," said Loureiro.

Analysis performed during the incubation period showed the occurrence of DNA alterations—both genetic (lesions that caused mutations in the nucleotide sequence) and epigenetic (increased levels of 5-methylcytosine, which alters gene expression). Cells grown in the semi-solid medium displayed global hypomethylation (reduction in levels of 5-methylcytosine), a characteristic of tumor cells.

Supplementing cells exposed to the carcinogen with nicotinamide riboside yielded positive results since they proved unable to grow in the agar medium, displaying similar behavior to the control cells, which were not exposed to benzo[a]pyrene.

Explore further: 'Epigenetic' changes from cigarette smoke may be first step in lung cancer development

Related Stories

'Epigenetic' changes from cigarette smoke may be first step in lung cancer development

September 11, 2017
Scientists at the Johns Hopkins Kimmel Cancer Center say they have preliminary evidence in laboratory-grown, human airway cells that a condensed form of cigarette smoke triggers so-called "epigenetic" changes in the cells ...

Preclinical study suggests E-cigarettes may promote lung cancer in high-risk individuals

January 9, 2014
Exposing human lung cells with genetic mutations associated with high risk for lung cancer to the chemicals in electronic-cigarette (e-cigarette) vapor enhanced the cells' cancerous behaviors, according to preliminary results ...

Altered primary chromatin structures and their implications in cancer development

April 26, 2016
Cancer development is a complex process involving both genetic and epigenetic changes. Genetic changes in oncogenes and tumor-suppressor genes are generally considered as primary causes, since these genes may directly regulate ...

Recommended for you

Single-cell study in a childhood brain tumor affirms the importance of context

April 20, 2018
In defining the cellular context of diffuse midline gliomas, researchers find the cells fueling their growth and suggest a potential approach to treating them: forcing their cells to be more mature.

Aggressive breast cancer already has resistant tumour cells prior to chemotherapy

April 20, 2018
Difficult to treat and aggressive "triple-negative" breast cancer is chemoresistant even before chemotherapy begins, a new study by researchers from Karolinska Institutet and the University of Texas MD Anderson Cancer Center ...

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.