Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development

Nicolella, Heloiza Diniz; Assis, Sônia de

doi:10.3390/ijms23094671

Cited by 28 publications

(13 citation statements)

References 109 publications

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“…Considering the protective effect of antioxidants against cancer and the pro-tumor effects of TNF- α , this scenario represents a disbalance that can stimulate cell proliferation, DNA damage, and immune deregulation, favoring BC development. It is important to highlight that pesticides, including those reported here in our study area, are pointed out as endocrine disruptors ( 43 – 46 ), an event intrinsically linked to deregulated immunological and inflammatory responses ( 9 ) that could confer some carcinogenic potential to such substances. Our findings strengthen several worldwide studies demonstrating augmented breast cancer risk in pesticide occupationally exposed women ( 47 – 55 ) by adding information about possibly implicated mechanisms in the pre-carcinogenic stages.…”

Section: Discussionmentioning

confidence: 90%

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue

da Silva,

Ferreira,

Komori

et al. 2023

Front. Public Health

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Studies have documented the high occurrence of several tumors, including female breast cancer, in populations occupationally exposed to pesticides worldwide. It is believed that in addition to direct DNA damage, other molecular alterations that indicate genomic instability are associated, such as epigenetic modifications and the production of inflammation mediators. The present study characterized the profile of inflammatory changes in the breast tissue of women without cancer occupationally exposed to pesticides. In samples of normal breast tissue collected during biopsy and evaluated as negative for cancer by a pathologist, oxidative stress levels were assessed as inflammatory markers through measurements of lipoperoxides and total antioxidant capacity of the sample (TRAP) by high-sensitivity chemiluminescence, as well as levels of nitric oxide (NOx) metabolites. The levels of inflammation-modulating transcription factors PPAR-γ (peroxisome proliferator-activated receptor gamma) and NF-κB (nuclear factor kappa B) were also quantified, in addition to the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12). The levels of lipoperoxides, TRAP, and NOx were significantly lower in the exposed group. On the other hand, PPAR-γ levels were increased in the breast tissue of exposed women, with no variation in NF-κB. There was also a rise of TNF-α in exposed women samples without significant variations in IL-12 levels. These findings suggest an inflammatory signature of the breast tissue associated with pesticide exposure, which may trigger mechanisms related to mutations and breast carcinogenesis.

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Section: Discussionmentioning

confidence: 90%

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue

da Silva,

Ferreira,

Komori

et al. 2023

Front. Public Health

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“…In addition, although the risks of pesticide exposure have been vastly evaluated, the transgenerational effects of these exposures need more attention. It has been shown that the environmentally induced disease risk can be transmitted to the offspring, via epigenetic mechanisms through female and male germ lines [ 199 ].…”

Section: Discussionmentioning

confidence: 99%

Environmental Pollution and Risk of Childhood Cancer: A Scoping Review of Evidence from the Last Decade

Navarrete-Meneses,

Salas-Labadía,

Gómez-Chávez

et al. 2024

IJMS

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The long-term effects of environmental pollution have been of concern as several pollutants are carcinogenic, potentially inducing a variety of cancers, including childhood cancer, which is a leading cause of death around the world and, thus, is a public health issue. The present scoping review aimed to update and summarize the available literature to detect specific environmental pollutants and their association with certain types of childhood cancer. Studies published from 2013 to 2023 regarding environmental pollution and childhood cancer were retrieved from the PubMed database. A total of 174 studies were eligible for this review and were analyzed. Our search strategy brought up most of the articles that evaluated air pollution (29%) and pesticides (28%). Indoor exposure to chemicals (11%), alcohol and tobacco use during pregnancy (16%), electromagnetic fields (12%), and radon (4%) were the subjects of less research. We found a particularly high percentage of positive associations between prenatal and postnatal exposure to indoor (84%) and outdoor (79%) air pollution, as well as to pesticides (82%), and childhood cancer. Positive associations were found between leukemia and pesticides and air pollution (33% and 27%); CNS tumors and neuroblastoma and pesticides (53% and 43%); and Wilms tumor and other rare cancers were found in association with air pollution (50%). Indoor air pollution was mostly reported in studies assessing several types of cancer (26%). Further studies are needed to investigate the mechanisms underlying the potential associations between indoor/outdoor air pollution and pesticide exposure with childhood cancer risk as more preventable measures could be taken.

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“…While life-style factors such as obesity have been shown to alter sperm non-coding RNAs in men, 53 no human studies have directly investigated the link between environmental toxicants such as DDT and germline RNA changes to the best of our knowledge; though several reports in animal models exist. [54][55][56] Nonetheless, a number of epidemiological studies link parental environmental toxins and cancer in the progeny. For instance, an association between paternal exposure to pesticides and a number of childhood cancers in offspring has been reported.…”

Section: Discussionmentioning

confidence: 99%

Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model

Cruz

Dominguez

Chen

et al. 2023

Preprint

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DNA sequence accounts for the majority of disease heritability, including cancer. Yet, not all familial cancer cases can be explained by genetic factors. It is becoming clear that environmentally induced epigenetic inheritance occurs and that the progeny’s traits can be shaped by parental environmental experiences. In humans, epidemiological studies have implicated environmental toxicants, such as the pesticide DDT, in intergenerational cancer development, including breast and childhood tumors. Here, we show that the female progeny of males exposed to DDT in the pre-conception period have higher susceptibility to developing aggressive tumors in mouse models of breast cancer. Sperm of DDT-exposed males exhibited distinct patterns of small non-coding RNAs, with an increase in miRNAs and a specific surge in miRNA-10b levels. Remarkably, embryonic injection of the entire sperm RNA load of DDT-exposed males, or synthetic miRNA-10b, recapitulated the tumor phenotypes observed in DDT offspring. Mechanistically, miR-10b injection altered the transcriptional profile in early embryos with enrichment of genes associated with cell differentiation, tissue and immune system development. In adult DDT-derived progeny, transcriptional and protein analysis of mammary tumors revealed alterations in stromal and in immune system compartments. Our findings reveal a causal role for sperm RNAs in environmentally induced inheritance of cancer predisposition and, if confirmed in humans, this could help partially explain some of the “missing heritability” of breast, and other, malignancies.

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Epigenetic Inheritance: Intergenerational Effects of Pesticides and Other Endocrine Disruptors on Cancer Development

Cited by 28 publications

References 109 publications

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue

Brief research report pesticide occupational exposure leads to significant inflammatory changes in normal mammary breast tissue

Environmental Pollution and Risk of Childhood Cancer: A Scoping Review of Evidence from the Last Decade

Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model

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