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Molecular epidemiology of lung cancer and the modulation of markers of chronic carcinogen exposure by chemopreventive agents
Author(s) -
Perera Frederica P.,
Tang Deliang,
GrinbergFunes Ricardo A.,
Blackwood M. Anne,
Dickey Christopher,
Blaner William,
Santella Regina M.
Publication year - 1993
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240531017
Subject(s) - carcinogen , lung cancer , epidemiology , cancer research , medicine , oncology , cancer , lung , chemistry , biochemistry
Chronic inhalation exposure to environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs), cigarette smoke, 4‐aminobiphenyl (4‐ABP), ethylene oxide, and styrene is associated with elevations in biomarkers such as DNA adducts, protein adducts, sister chromatid exchanges (SCEs), chromosomal aberrations, gene mutation, and/or oncogene activation. These biomarkers indicate an increased cancer risk for the exposed population, although quantitative estimates cannot be made with certainty. There is convincing epidemiological evidence that the antioxidant and free radical‐scavenging vitamins C and E and β‐carotene (β‐C) protect against cancer of the lung and other epithelial tissues, with somewhat weaker evidence for retinol. Experimental studies demonstrate that these micronutrients are capable of blocking or reducing tumor formation caused by diverse carcinogens. A variety of mechanisms appear to be involved, including suppression of carcinogen activation, enhancement of carcinogen detoxification, induction of cellular differentiation, inhibition of mutagenesis, enhancement of immunologic function, and/or reduction of the formation of carcinogen–DNA adducts, SCEs, micronuclei, and other markers of genotoxic damage. Therefore, we have recently investigated the possible modifying effect of serum vitamins C and E, β‐C, and retinol on a number of such biomarkers in a case‐control study of lung cancer, and in a cross‐sectional study of heavy smokers. Preliminary results indicate an inhibitory effect of certain vitamins on DNA adduct formation. A significant number of human intervention trials are ongoing involving these vitamins. It appears that biomarkers can provide useful intermediate endpoints for assessment of both the mechanisms and the efficacy of chemopreventive agents.