Guide for the Care and Use of Laboratory Animals

https://zenodo.org/record/1253874/files/article.pdf

A simple technique for quantitation of low levels of DNA damage in individual cells

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.

Oxidants, oxidative stress and the biology of ageing.

Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis.

https://zenodo.org/record/1230948/files/article.pdf

p53 mutations in human cancers

http://academic.oup.com/jaoac/article-pdf/75/1/1/32454774/jaoac0001.pdf

Pollution, Pesticides, and Cancer

The public has numerous misconceptions about the relationship between environmental pollution and human cancer. Underlying these misconceptions is an erroneous belief that nature is benign. In this article we highlight eight of these misconceptions and describe the scientific information that undermines each one.

Misconceptions on Pollution and the Causes of Cancer

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, reduction of high occupational exposures, and reduced consumption of alcohol and possibly red meat. Risks of many forms of cancer can already be lowered, and the potential for further risk reduction is great. In the USA cancer death rates for all cancers combined are decreasing, if lung cancer — 90% of which is due to smoking — is excluded from the analysis (Ames et al., 1995). The focus of this chapter is prioritization of possible cancer hazards in the diet.

Prioritization of possible carcinogenic hazards in food

Review Article: Delaying the Mitochondrial Decay of Aging—a Metabolic Tune-up

The damage produced by endogenously generated oxygen radicals has been proposed as a major contributory factor to aging and the many degenerative processes associated with it, including cancer, heart disease, and cognitive dysfunction (1). Under physiological conditions, endogenous oxidants are produced at a high rate, resulting in extensive oxidative damage to proteins, lipids, and DNA (2–5). Oxidative damage to DNA, based on the urinary excretion of DNA adducts, occurs at an estimated rate of 105 hits/cell/d in the rat and about 104 hits/cell/d in the human (6) Evidence is accumulating to suggest that rates of cellular oxidative damage can also be modulated by exogenous factors. Oxidative insult to tissues is increased by smoking and exposure to ionizing radiation, and decreased by intake of antioxidants, such as ascorbate and tocopherols, that are part of endogenous antioxidant defenses (7–10). Hence, a critical determinant of the rate of cellular damage is the balance between antioxidant defense capacity and the oxidant insult to the tissue. Improved nutrition, increased intake of antioxidants, and cessation of dangerous habits, such as smoking, is critical for lowering individual risk of degenerative disease.

Bruce N. Ames

Papers

Pollution, Pesticides, and Cancer

Misconceptions on Pollution and the Causes of Cancer

Prioritization of possible carcinogenic hazards in food

Review Article: Delaying the Mitochondrial Decay of Aging—a Metabolic Tune-up

Nutritional Prevention of DNA Damage to Sperm and Consequent Risk Reduction in Birth Defects and Cancer in Offspring