Enhancement of pre-existing DNA adducts in rodents exposed to cigarette smoke

Citation
Rc. Gupta et al., Enhancement of pre-existing DNA adducts in rodents exposed to cigarette smoke, MUT RES-F M, 424(1-2), 1999, pp. 195-205
Citations number
76
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
ISSN journal
1386-1964 → ACNP
Volume
424
Issue
1-2
Year of publication
1999
Pages
195 - 205
Database
ISI
SICI code
1386-1964(19990308)424:1-2<195:EOPDAI>2.0.ZU;2-1
Abstract
Exposure to tobacco smoke has been implicated in the increased incidence of cancer and cardiovascular diseases. This report describes various experime ntal studies in animals that were carried out to determine the ability of c igarette smoke to form DNA adducts and to define chromatographic nature of the major adducts. Tissues from rodents exposed to mainstream or sidestream cigarette smoke in nose-only and whole-body exposure systems, respectively , for different durations were analyzed for DNA adducts by P-32-postlabelin g assay. The results showed essentially similar qualitative patterns in var ious respiratory (lung, trachea, larynx) and non-respiratory (heart, bladde r) tissues of smoke-exposed rats. However, adduct pattern in the nasal muco sa was different. The mean total DNA adducts in various tissues expressed a s per 10(10) nucleotides exhibited the following order: heart (700)> lung ( 420)> trachea (170)> larynx (150)> bladder (50). Some qualitatively identic al adducts were routinely detected in tissues from sham-treated rats but at greatly reduced levels (5- to 25-fold). The levels of lung DNA adducts inc reased with the duration of exposure up to 23 weeks and returned to control levels 19 weeks after the cessation of exposure. Species-related differenc es in adduct magnitude and patterns were observed among rats, mice and guin ea pigs; mouse being the most sensitive to DNA damage and guinea pig the le ast sensitive. Whole-body exposure of rats to sidestream cigarette smoke al so enhanced the pre-existing DNA adducts by several fold in different tissu es. Selective chromatography, and extractability in butanol suggested lipop hilic nature of smoke-associated DNA adducts, which were, however, recovere d significantly better in nuclease pi than butanol enrichment procedure. Th e major smoke-associated adducts were chromatographically different from an y of the reference adducts of polycyclic aromatic hydrocarbons (PAHs) co-ch romatographed with the smoke DNA samples. Because PAH-DNA adducts are recov ered with equal efficiency by the two enrichment procedures, the above obse rvations suggested that smoke-associated adducts are not related to typical PAHs, like benzo[a]pyrene. It is concluded that cigarette smoke increased the levels of pre-existing endogenous DNA adducts (the so-called I-compound s) in animal models and that these adducts are unrelated to those formed by typical PAHs. (C) 1999 Elsevier Science B.V. All rights reserved.