TY - JOUR
T1 - Molecular epidemiology of lung cancer and the modulation of markers of chronic carcinogen exposure by chemopreventive agents
AU - Perera, Frederica P.
AU - Tang, Deliang
AU - Grinberg‐Funes, Ricardo A.
AU - Blackwood, M. Anne
AU - Dickey, Christopher
AU - Blaner, William
AU - Santella, Regina M.
PY - 1993
Y1 - 1993
N2 - 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.
AB - 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.
KW - biomarkers
KW - chemoprevention
KW - lung cancer
KW - molecular epidemiology
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U2 - 10.1002/jcb.240531017
DO - 10.1002/jcb.240531017
M3 - Article
C2 - 8412183
AN - SCOPUS:0027358264
SN - 0730-2312
VL - 53
SP - 119
EP - 128
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - S17F
ER -