Effects of GSTT1 and GSTM1 polymorphisms in glutathione levels and breast cancer development in Brazilian patients

Pacholak, Letícia Madureira; Kern, Rodrigo; Oliveira, Stefania Tagliari de; Lúcio, Léia Carolina; Amarante, Marla Karine; Guembarovski, Roberta Losi; Watanabe, Maria Angélica Ehara

doi:10.1007/s11033-020-06107-w

Cited by 8 publications

(6 citation statements)

References 43 publications

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“…It is unclear what drives the lower level of εdAdo adducts in individuals who are GSTM1 null. GSTM1 is not the only or most efficient GST involved in the detoxification of lipid peroxidation products. − GSH is a critical molecule in the detoxification of many toxicants, including lipid peroxidation products, and its levels and the activity of GSTs and glutathione peroxidases influence these pathways. The interplay of the regulation of these pathways is complicated, and their influence on the level of εdAdo adducts is unclear.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer

Park

Marchand

Cheng

et al. 2022

Chem. Res. Toxicol.

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The Multiethnic Cohort Study has demonstrated that the risk for lung cancer in cigarette smokers among three ethnic groups is highest in Native Hawaiians, intermediate in Whites, and lowest in Japanese Americans. We hypothesized that differences in levels of DNA adducts in oral cells of cigarette smokers would be related to these differing risks of lung cancer. Therefore, we used liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry to quantify the acrolein-DNA adduct (8R/S)-3-(2′-deoxyribos-1′-yl)-5,6,7,8-tetrahydro-8-hydroxypyrimido[1,2-a]purine-10(3H)-one (γ-OH-Acr-dGuo, 1) and the lipid peroxidation-related DNA adduct 1,N 6 -etheno-dAdo (εdAdo, 2) in DNA obtained by oral rinse from 101 Native Hawaiians, 101 Whites, and 79 Japanese Americans. Levels of urinary biomarkers of nicotine, acrolein, acrylonitrile, and a mixture of crotonaldehyde, methyl vinyl ketone, and methacrolein were also quantified. Whites had significantly higher levels of γ-OH-Acr-dGuo than Japanese Americans and Native Hawaiians after adjusting for age and sex. There was no significant difference in levels of this DNA adduct between Japanese Americans and Native Hawaiians, which is not consistent with the high lung cancer risk of Native Hawaiians. Levels of εdAdo were modestly higher in Whites and Native Hawaiians than in Japanese Americans. The lower level of DNA adducts in the oral cells of Japanese American cigarette smokers than Whites is consistent with their lower risk for lung cancer. The higher levels of εdAdo, but not γ-OH-Acr-dGuo, in Native Hawaiian versus Japanese American cigarette smokers suggest that lipid peroxidation and related processes may be involved in their high risk for lung cancer, but further studies are required.

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Section: Discussionmentioning

confidence: 99%

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer

Park

Marchand

Cheng

et al. 2022

Chem. Res. Toxicol.

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“…Breast cancer is a disease characterized by an extensive systemic inflammatory response that includes variations in cytokines, immune signaling mediators, and oxidative stress metabolite levels [ 23 , 24 , 25 , 26 ]. In particular, investigating patients’ immunological profiles has emerged as a point of interest over the years.…”

Section: Discussionmentioning

confidence: 99%

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

Silva

Scandolara

Kern

et al. 2022

Cancers

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Breast cancer risk stratification is a strategy based using on clinical parameters to predict patients’ risk of recurrence or death, categorized as low, intermediate, or high risk. Both low and high risk are based on well-defined clinical parameters. However, the intermediate risk depends on more malleable parameters. It means an increased possibility for either suboptimal treatment, leading to disease recurrence, or systemic damage due to drug overload toxicity. Therefore, identifying new factors that help to characterize better the intermediate-risk stratification, such as environmental exposures, is necessary. For this purpose, we evaluated the impact of occupational exposure to pesticides on the systemic profile of cytokines (IL-12, IL-4, IL-17A, and TNF-α) and oxidative stress (hydroperoxides, total antioxidants, and nitric oxide metabolites), as well as TGF-β1, CTLA-4, CD8, and CD4 expression, investigated in tumor cells. Occupational exposure to pesticides decreased the levels of IL-12 and significantly increased the expression of TGF-β1 and CTLA-4 in the immune infiltrate. Nevertheless, we observed a decrease in CTLA-4 in tumor samples and CD8 in infiltrating cells of intermediate overweight or obese patients with at least one metastatic lymph node at the diagnosis. These findings indicate that occupational exposure to pesticides changes the molecular behavior of disease and should be considered for intermediate-risk stratification assessment in breast cancer patients.

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“…(7) TNBC does not express the receptor of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor-2 (HER2) which causes chemotherapy to be the first recommended therapy. (5) A meta-analysis study showed that GSTM1 deletion may increase the risk of breast cancer in Asian, Caucasian, and postmenopausal women. GSTM1 null causes chemotherapy exported by the cells.…”

Section: Introductionmentioning

confidence: 99%

GSTM1 Deletion Compensated in mRNA Expression and 4T1 Viability After Editing Using CRISPR/Cas9 Single and Double gRNA

Arsita

Nugrahaningsih

Sadewa³

2023

Indones Biomed J

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BACKGROUND: Glutathione S-transferase Mu-1 (GSTM1) is known to undergo polymorphism and plays role in drug metabolism including Paclitaxel (PTX), the first-line chemotherapy for breast cancer. However, the effect of GSTM1 polymorphism against chemotherapy in breast cancer is limited and unexplored. This study was conducted to explore the effects of single and double guide (gRNA) on the GSTM1 knocked out (KO) and its effect on the response of PTX in the 4T1 cell line.METHODS: The preparatory stage was done by culturing and electroporating 4T1 cells using Ribonucleoprotein of clustered regularly interspaced short palindromic repeats (CRISPR)/Caspase 9 (Cas9). KO validation was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Sanger sequencing, and ICE analysis. The 4T1 viability was examined by MTT Assay.RESULTS: The number of base pairs of GSTM1 after being engineered by single or double gRNA was 86 bases. The DNA quantity of GSTM1 engineered by gRNA was more than using double gRNAs. The mRNA expression of GSTM1 engineered by single gRNA was lower than using double gRNAs. IC50 values of PTX between wildtype and KO were not significantly different, in the range of 30 µM.CONCLUSION: The base-pair length of GSTM1 exon 4 that is knocked out with single and double gRNA have the same number of base pairs. The quantity of GSTM1 DNA and mRNA expression are contrary between single gRNA and double gRNA, and IC50 PTX values in the 4T1 cell line of the control group with single or double gRNA knocked out do not differ markedly. PTX efficiency as chemotherapy is not disturbed in the GSTM1 deletion genetic profile.KEYWORDS: GSTM1, gRNA, Paclitaxel, CRISPR, breast cancer

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Effects of GSTT1 and GSTM1 polymorphisms in glutathione levels and breast cancer development in Brazilian patients

Cited by 8 publications

References 43 publications

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer

Quantitation of DNA Adducts Resulting from Acrolein Exposure and Lipid Peroxidation in Oral Cells of Cigarette Smokers from Three Racial/Ethnic Groups with Differing Risks for Lung Cancer

Occupational Exposure to Pesticides Affects Pivotal Immunologic Anti-Tumor Responses in Breast Cancer Women from the Intermediate Risk of Recurrence and Death

GSTM1 Deletion Compensated in mRNA Expression and 4T1 Viability After Editing Using CRISPR/Cas9 Single and Double gRNA

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