Uterine fibroid growth increases with cadmium exposure, but not because cadmium acts like estrogen

Breathing or eating even small amounts of the toxic metal cadmium—a widespread contaminant of cigarettes and seafood—may increase a woman’s risk for developing uterine fibroids, but not in the way scientists previously thought. By the age of 50, at least seven out of ten American women will have developed these benign tumors that can cause infertility and miscarriage. Scientists have long suspected that cadmium encourages fibroid growth by mimicking the natural hormone estrogen. However, new research published this month in Environmental Health Perspectives indicates that cadmium may instead encourage fibroid growth through a molecular pathway involved in a third of all tumors. The North Carolina researchers suggest that treatments targeting this pathway may block cadmium’s dangerous effects, and help limit the growth and damage of uterine fibroids in women.

To figure out how cadmium encourages fibroid growth, the researchers added it to different types of uterus-like cells grown in Petri dishes. When they grew the cells with low concentrations of cadmium—concentrations similar to the cadmium blood levels of more than 70% of Americans—they found that the metal greatly increased the number of cells, similar to how estrogen increases the number of uterus cells. But the similarity stopped there: while estrogen increased cell growth by interacting with estrogen receptors—molecules on a cell’s surface which relay signals to its nucleus, thereby affecting which genes turn on and off—the cadmium did not interact with the estrogen receptors.

So how was cadmium increasing the uterus cells’ growth? The researchers figured out the answer when they looked at other molecules involved in cell signaling—specifically, the MAPK pathway, a series of signal molecules involved in both healthy cell growth and cancerous cell growth. When they exposed the uterus cells simultaneously to cadmium and to chemicals that interfere with the MAPK pathway, they found that cadmium couldn’t increase cell growth. While cadmium didn’t increase cell growth by interacting with estrogen receptors, the researchers suggested that it may act together with estrogen naturally present in a woman’s body (or estrogen-like molecules such as bisphenol A) to increase fibroid growth more than cadmium or estrogen alone could.

Reference:
Gao X, Yu L, Moore AB, Kissling GE, Waalkes MP, & Dixon D (2015). Cadmium and Proliferation in Human Uterine Leiomyoma Cells: Evidence of a Role for EGFR/MAPK Pathways but Not Classical Estrogen Receptor Pathways. Environmental health perspectives, 123 (4), 331-6 PMID: 25343777

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Arsenic, cadmium, and lead: A toxic trinity of risk factors for Alzheimer’s disease?

ResearchBlogging.orgA modern cause of Alzheimer’s disease may lie in the ancient poisons of arsenic, lead, and cadmium. Indian researchers recently reported that young rats exposed to water contaminated with these toxic metals developed symptoms of Alzheimer’s disease, a form of dementia affecting more than 25 million people worldwide. Disturbingly, rats which drank water contaminated with all three metals–water similar to that drank by many Indian people–developed much worse symptoms than rats which drank water with fewer metals. The researchers cautioned that people who drink contaminated water during childhood may develop symptoms of Alzheimer’s disease decades earlier than normal.

How do three ancient poisons work together to create such a potent brew? To tease out the answer, the researchers examined the toxic effects of each metal alone, and the effects of different combinations. Compared to arsenic and cadmium, lead provoked the rats’ brains to make more amyloid-beta–the sticky protein which congeals into plaques in the brains of Alzheimer’s patients. Rats which consumed lead with arsenic had even more amyloid-beta. But when rats consumed lead with arsenic and cadmium, the three metals acted synergistically–the toxic equivalent of shouting into a bullhorn hooked up to an amplifier. The metals amplified each other’s damage to the rats’ brains, and even caused the brains to become inflamed.

With their damaged brains, the rats were worse at figuring out a maze. They were losing their ability to learn and remember–just like humans with Alzheimer’s disease.

Citation:
Ashok A, Rai NK, Tripathi S, & Bandyopadhyay S (2014). Exposure to As-, Cd-, and Pb-Mixture Induces Aβ, Amyloidogenic APP Processing and Cognitive Impairments via Oxidative Stress-Dependent Neuroinflammation in Young Rats. Toxicological sciences : an official journal of the Society of Toxicology PMID: 25288670