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Weinhouse Lab

@weinhouselab.bsky.social

OHSU faculty. Research in epigenetic memory of environmental stress response

24 Followers  |  57 Following  |  2 Posts  |  Joined: 10.01.2026  |  1.3229

Latest posts by weinhouselab.bsky.social on Bluesky

In vitro evidence for bisphenol A as a human liver carcinogen: Environmentally relevant doses inhibit cancer-protective ESR1 signaling in a human liver cell line Several environmentally ubiquitous endocrine disrupting chemicals (EDCs) are suspected carcinogens, but their mechanism(s) of action are unknown. In this study, we test the potential for a model EDC, bisphenol A (BPA), to both initiate (via oxidative mutagenesis) and promote (via endocrine disruption) liver carcinogenesis. This study is motivated by our prior finding that developmental BPA exposure caused hepatocellular carcinoma (HCC) in mice. Here, we provide in vitro evidence supporting a mechanism for BPA as a non-genotoxic carcinogen. Using a highly sensitive, error-corrected sequencing method, we demonstrate that human population-relevant doses of BPA cause mutations that are consistent with oxidative DNA damage; however, overall mutation frequency does not differ substantially from controls. In contrast, we show that BPA inhibits cancer-protective, estrogen-induced transcription of estrogen receptor 1 (ESR1) target genes in the presence of pre-pubertal, but not post-pubertal, levels of estradiol. These results constitute strong initial evidence supporting BPA as a liver cancer promoting agent. This mechanism may be generalizable to a wide range of environmental EDCs that are weak agonists for ESR1. This finding is critically important to prevention of HCC, which is prevalent, lethal, and poorly responsive to therapy. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Environmental Health Sciences, R01ES034836 Oregon Institute of Occupational Health Sciences, OHSU

Our second pre-print of the new year:

We show that bisphenol A inhibits cancer-protective, estrogen-induced transcription of estrogen receptor 1 (ESR1) target genes in the presence of pre-pubertal, but not post-pubertal, levels of estradiol in HepG2 cells.

www.biorxiv.org/content/10.6...

30.01.2026 22:37 — 👍 2    🔁 0    💬 0    📌 0
Epigenetic plasticity is a driver of heritable pollution tolerance in Atlantic killifish Heritable epigenetic adaptation to environmental stressors is a compelling but highly contested possibility. Previously, we showed evidence of a generationally heritable epigenetic memory at the cytochrome P450 1a ( cyp1a ) gene in wild Atlantic killifish ( Fundulus heteroclitus ) with acquired tolerance to polycyclic aromatic hydrocarbons (PAHs). This memory leads to blunted induction of cyp1a by PAHs; this blunted response protects against PAH-induced cancer. Here, using Oxford Nanopore long-read sequencing in PAH-tolerant and -sensitive F. heteroclitus embryos, we show that PAH-tolerant embryos displayed reduced plasticity in DNA methylation response to PAH, as compared to PAH-sensitive embryos, that was not due to mutational loss of CpG sites. Notably, we observed population differences in DNA methylation of genes in pathways linked to the PAH tolerance phenotype, including aryl hydrocarbon receptor (ahr) and voltage-gated potassium channel signaling, as well as developmental processes and energy metabolism. Specifically, we observed PAH-induced loss of cyp1a gene body methylation in PAH-sensitive but not-tolerant embryos. We observed similar patterns at cyp1b1 , cyp1c1 , and the aryl hydrocarbon receptor repressor, ahrr, which show similarly blunted expression in response to PAH challenge. The reduced loss in genic methylation in tolerant embryos was correlated with greater induction of natural anti-sense RNA transcripts in cis ( cis -NATs), which may regulate transcription of these genes. Our data support the existence of stable epigenetic responses to chronic environmental stressors in a natural experimental setting, with broad implications for natural or directed adaptation strategies for other populations. ### Competing Interest Statement The authors have declared no competing interest.

Our latest research is on biorxiv!

We show that acquired pollution tolerance tracks with generationally heritable DNA methylation signatures in tolerance-linked pathways.

"Epigenetic plasticity is a driver of heritable pollution tolerance in Atlantic killifish"
www.biorxiv.org/content/10.6...

30.01.2026 22:11 — 👍 3    🔁 1    💬 0    📌 1

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