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Biological Chemistry

Chemistry’s Role In Cancer

February 16, 2015 | A version of this story appeared in Volume 93, Issue 7

Jan. 12, page 4: The image caption in the graphene oxide article incorrectly states that the top row of photos shows stable graphene oxide films. The bottom row actually depicts the stable films, and the top row depicts films degraded by water.

Feb. 2, page 20: The number of recharge cycles for supercapacitors is misstated in the table. They offer up to 1 million recharge cycles.

“Chemistry Year in Review” outlined some important achievements of chemistry in 2014 (C&EN, Dec. 22, 2014, page 14). This letter is to point out that chemistry plays the central role in the ­etiology and prevention of the most ­prevalent types of human cancer. The chemical agents responsible for the initiation of cancer are the estrogens. They become carcinogenic when their unbalanced metabolism in our bodies generates excessive amounts of estrogen-3,4-quinones.

When that happens, the estrogen-3,4-quinones react with DNA, forming depurinating estrogen-DNA adducts that generate the mutations leading to the initiation of cancer. We have demonstrated this for five different types of human cancer: breast, ovarian, and thyroid for women and prostate and non-Hodgkin lymphoma for men. We also think that other prevalent types of cancer are initiated by the same mechanism. This mechanism can be prevented by use of natural compounds such as resveratrol and N-acetylcysteine to block formation of estrogen-DNA ­adducts.

When we began conducting cancer research in the 1970s, chemical carcinogenesis played a relevant role in cancer research, supported by the National Cancer Institute. Unfortunately, appreciation of the role of chemistry in carcinogenesis was lost, and NCI dissolved the chemical carcinogenesis branch.

Meanwhile, we discovered that the potent polycyclic aromatic hydrocarbon carcinogens formed predominantly depurinating PAH-DNA adducts that generate cancer-initiating mutations (Proc. Natl. Acad. Sci. USA10422), and then we found that the depurinating estrogen-DNA adducts are also responsible for cancer-initiating mutations. The discovery of the importance of these depurinating DNA adducts has been neglected for the past 20 years. The final tragedy of this neglect is that chemistry also provides the pathway to cancer prevention. By using natural compounds such as resveratrol and N-acetylcysteine to prevent the formation of estrogen-DNA adducts, the transformation of cells to malignancy is also prevented.

With all of the great advances chemistry has provided for humankind, cancer research is one more area in which chemistry can enhance life and remove misery—if this is recognized by scientists.

Ercole Cavalieri
Eleanor Rogan
Eppley Institute for Research in Cancer & Allied Diseases



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