DNA damage and cancer

Research conducted here at The Institute of Cancer Research in the 1950s and 1960s provided the first conclusive evidence indicating that damage to DNA is the root cause of cancer.

Cancer cells replicate at an accelerated rate, often ignoring the normal controls on cell division and growth. Proteins within cells regulate growth and division, and were widely assumed to be the targets for cancer-causing chemicals. However, research conducted at the ICR by Professor Philip Lawley and Professor Peter Brookes showed that cancer is caused by damage not to proteins but to DNA.

Their discovery was made through working on mustard gas – which was known to cause cancer. In 1960, Professors Lawley and Brookes published a paper which showed that mustard gas reacted with both pure DNA and with the DNA of mice when injected into tumours.

In 1964, Professors Lawley and Brookes published their second classic paper. This used radiolabelled poly-aromatic hydrocarbons (PAHs), which are among the chemicals that give cigarettes their cancer-causing properties. They found a direct correlation between a PAH’s ability to induce tumours when applied to mouse skin, and the degree to which it bound to DNA. There was no correlation with the degree to which the PAH bound to proteins. It was this finding that showed that cancer was caused by chemicals damaging DNA rather than proteins.

This discovery marked a turning point for cancer research, and is the basis of all modern cancer research and treatment. It explains why some cancers can be inherited, enabling people with a particularly high risk of developing certain cancers to be identified. It has also changed the way that scientists search for new cancer drugs, allowing personalised treatments to be developed that target the specific genetic defects in an individual’s cancer.

Brookes and Lawley (1960) The reaction of mustard gas with nucleic acids in vitro and in vivo, Biochem. J., 77, 478–484

Brookes and Lawley (1964) Evidence for the Binding of Polynuclear Aromatic Hydrocarbons to the Nucleic Acids of Mouse Skin: Relation between Carcinogenic Power of Hydrocarbons and their Binding to Deoxyribonucleic Acid, Nature 202, 781 – 784 doi:10.1038/202781a0