Introduction

A majority of chemical carcinogens, either man-made or natural, exert their biological effects through interaction with DNA. The covalent reaction between an electrophilic carcinogen and a nucleophilic site in DNA leads to formation of modified nucleotides or DNA adducts. In addition to DNA-reactive chemicals, ionizing radiation and the ultraviolet (UV) light component of a natural sunlight form specific DNA lesions. Exogenously induced DNA adducts are a threat to genome integrity and are thought to be critical initiating factors in tumorigenesis, at least for some cancers.1-5 There has been growing realization that adducts formed from endogenous sources may possess similar if not higher mutagenic potential.6 Complex cellular DNA repair systems have evolved to remove DNA adducts from the genome thus counteracting a constant challenge to DNA encountered by all living species. These repair processes result in a consistent reduction of the cellular levels of DNA adducts. However, if unrepaired damage is still present during DNA replication, it may either cause DNA polymerases to stop at the site of a lesion (resulting in premature termination of replication, cell growth arrest, cytotoxicity, or chromosomal aberrations), or the polymerase will bypass the altered base with the possibility of base misincorporation and mutagenesis.7,8 DNA adducts may also undergo hydrolysis forming an abasic site and increasing the probability of strand scission and mutagenesis.6 The resulting genetic alterations may lead to creation of a new phenotype and, if growth controlling genes are involved, to cellular transformation and the development of tumors. Protooncogenes and tumor suppressor genes are critical targets for carcinogens.7,9 Identification of a link between DNA damage and mutations will strengthen the understanding to what extent elements of the environment are responsible for initiation of tumorigenesis in humans.

DNA adducts induced by different carcinogens may have significantly different mutational efficiencies. The steady-state levels of DNA adducts in human target tissues following chronic exposure to carcinogens are found to be dose-dependent and, in some cases, predictive of cancer inci-dence.1,5,10,11 One of the goals of these studies has been the development of preventive intervention methods to lower the human health impact from carcinogen exposures of environmental (including dietary), occupational, or clinical origin.

Over the last two decades, several sufficiently sensitive technologies have been developed to measure protein and DNA adducts at levels consistent with environmental and occupational exposure to genotoxic agents. However, the progress in this area faces the difficulties of accurate interpretation of the adduct type, individual and, importantly, interlaboratory variabilities in quantitative measurements. A plethora of published results notwithstanding, more data have to be obtained in order to establish a better correlation between the levels of adducts and specific types of cancer. Further methodological advances are necessary to make analytical methods more amenable to molecular epidemiological studies.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment