Human cancer: etiologic agents/dose responses/DNA repair/cellular and animal models.
The observation of cancer in an individual does not identify the causative agent(s). However, epidemiological data on populations do indicate that a large fraction of human cancers are associated with lifestyle/diet. Such studies may also help identify the etiologic agents but unless there are good dose-response data for humans and/or animal models, the probability of identifying the agent is not high. Cancers may result from endogenous reactions, such as oxidations or from exogenous agents, such as tobacco smoke (lung cancer), sunlight exposure (skin cancer), aflatoxin (liver cancer), and relatively high doses of ionizing radiations (many types of cancers). Many carcinogenic chemicals have been identified in the workplace but, they usually do not affect the overall population. Most cancer causing agents affect cellular DNA and change its coding specificity and act as cancer initiators. The repair of DNA damage ameliorates most of these endogenous and exogenous changes. The important role of DNA repair in controlling the induction of human cancer came from the observation that individuals with the skin cancer-susceptible, human disease xeroderma pigmentosum (XP) were defective in nucleotide excision repair. Endogenous DNA damages are usually damages to individual bases and are usually repaired by systems of glycosylases and endonucleases. It should be useful to investigate the rates of appearance of tumors in normal mice and in mice knocked out for specific repair enzymes because such mice could be used to test the roles of diet and caloric input in affecting particular types of endogenous damages.
Setlow
R B
RB
Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA. setlow@bnl.gov
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity; D004260:DNA Repair; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D002149:Energy Intake; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics
D002273:Carcinogens; D002274:Carcinogens, Environmental