Cancer mutations and

Knudson AG, Jr. (1971) Mutation and cancer statistical study of retinoblastoma. Proc Natl Acad Sci USA 68 820-823... 

Cigarette smoke contains aryl hydrocarbons such as benzo[a]pyrene that, once metabolized to reactive compounds, can form alkyl adducts of DNA bases leading to mutations and cancers of the lung and many other organs. 

Rosenkranz, H. S., Mutagenic Nitroarenes, Diesel Emissions, Particulate-Induced Mutations and Cancer An Essay on Cancer-Causation by a Moving Target, Mutat. Res., 367, 65-72 (1996). 

Loeb LA, Loeb KR, Anderson JP. Multiple mutations and cancer. Proc Natl Acad Sci USA 2003 100 776-781. 

As already indicated, the repair processes may inadvertently contribute to errors leading to mutation and more serious endpoints. Some chemicals can affect the repair process, so increasing mutation rates. Lack of a repair system also leads to increased mutations and cancer as occurs in patients suffering from the disease xerodermum pigentosum. These individuals are unable to remove thymidine dimers formed by exposure to ultraviolet light in the DNA of skin cells. They consequently suffer a very high incidence of skin cancer. 

Ames BN. Identifying environmental chemicals causing mutations and cancer. Science 1979 204 587-593. A classic article. 

Figure 7.3 The interaction (arylation) of guanine on the N2 position with the reactive metabolite of benzofa] pyrene, leading to an adduct believed to be responsible for mutation and cancer.

MOOLGAVKAR, S.H. and KNUDSON, A.G. (1981). Mutation and cancer A model for human carcinogenesis, J. Natl. Cancer Inst. 66, 1037-1052. 

The DNA alterations described above have involved covalent bonding of groups to nitrogenous bases. Another type of interaction is possible with highly planar (flat) molecules that are able to fit between base pairs (somewhat like slipping a sheet of paper between pages of a book), a phenomenon called intercalation. This can cause deletion or addition of base pairs, leading to mutation and cancer. A compound known to cause this phenomenon is 9-aminoacridine ... 

Relationship between mutations and cancer, Theodor Bovery (1914) ... 

ROBERT SHAPIRO is professor emeritus and senior research scientist in the Department of Chemistry at New York University. His research has centered on the chemistry of nucleic acids, with emphasis on the reactions of DNA and RNA with carcinogens and mutagens. Dr. Shapiro is author or co-author of over 110 publications, primarily in the area of DNA chemistry. In particular, he and his co-workers have studied the ways in which environmental chemicals can damage our hereditary material, causing changes that can lead to mutations and cancer. 

How the natural toxin aflatoxin, produced by a fungus, damages DNA. The aflatoxin is converted into a reactive produa in the liver that interacts with components of DNA (the bases A, T, C, G). This changes the base code, leading to mutations and cancer. 

S. H. Moolgavkar and A. G. Knudson, Mutation and Cancer A Model for Human Carcinogenesis, Journal of National Cancer Institute, 66, 1037-1052 (1981). 

This challenging problem is also vital for current research on oxidative damage of DNA, which may cause apoptosis, mutations, and cancer. 

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