Carcinogenesis
-
Randomized Controlled Trial Clinical Trial
Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans.
A high intake of glucosinolate-containing cruciferous vegetables, such as Brussels sprouts (Brassica oleraceae), has been linked to a decreased cancer risk, but the underlying mechanism is still unclear. The aim of this study was to reveal possible modulating effects of consumption of Brussels sprouts on duodenal, rectal and lymphocytic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content. Ten healthy non-smoking volunteers were randomly assigned to two groups in a cross-over design. ⋯ GSH contents were uninfluenced by the dietary regimen. In conclusion, consumption of glucosinolate-containing Brussels sprouts for 1 week results in increased rectal GST-alpha and -pi isozyme levels. We hypothesize that these enhanced detoxification enzyme levels may partly explain the epidemiological association between a high intake of glucosinolates (cruciferous vegetables) and a decreased risk of colorectal cancer.
-
Comparative Study
Occupational exposure to unburnt bidi tobacco elevates mutagenic burden among tobacco processors.
The nature of mutagenic burden due to occupational exposure to tobacco flakes and dust was determined among 20 female tobacco processors (TP) and 20 matched controls (C) by testing urinary mutagenicity in the Ames assay. In addition, urinary cotinine was estimated as a marker of tobacco absorption. Workers and controls were sub-divided into those with no tobacco habit (NH) and those habituated to the use of masheri (a pyrolysed form of tobacco) as a dentifrice (MH). ⋯ Generally, beta-glucuronidase treatment reduced or abolished the mutagenic potential of workers' urine samples indicating that glucuronide conjugates may have partially contributed to direct mutagenicity. Experiments using scavengers of reactive oxygen species revealed that direct mutagenicity in TA102 strain was mediated mainly via hydroxyl radicals. The results clearly demonstrate that tobacco processors are exposed to a wide spectrum of mutagens that cause frame-shift, base pair substitution and oxidative damage.
-
Reduction of Cr(VI) by NADH and NADPH has been shown to yield Cr(V) species, which have been detected by electron paramagnetic resonance (EPR) spectroscopy. The fine structure on the EPR signal of the Cr(V) species is consistent with the presence of two NAD(P)H ligands in a square-pyramidal arrangement with a single oxygen (oxo) group at the apex. Neither this species nor the initial Cr(VI) complex damage DNA components as evidenced by the lack of effect of these compounds on the optical and EPR signals of the Cr(VI) and Cr(V) species respectively. ⋯ The signals from the former species are consistent with radical addition to the base, whereas the sugar-derived species are believed to be formed via hydrogen atom abstraction. In each case, this behaviour is consistent with hydroxyl radicals being the damaging species in systems where Cr(V) is generated in the presence of hydrogen peroxide. These results therefore suggest that it may be the hydroxyl radical that is the ultimate carcinogenic species in cells and systems exposed to Cr(VI).
-
The purpose of this study was to establish a lung tumor model for the evaluation of chemopreventive agents against lung cancer in smokers. Lung tumor induction in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (BaP) was studied using protocols in which these two tobacco smoke carcinogens were given individually or in combination. Groups of female A/J mice were treated by either intragastric gavage (i.g.) or by intraperitoneal injection (i.p.) with various doses of NNK and/or BaP for 8 consecutive weeks. ⋯ This regimen induced 10.5 +/- 4.4 lung adenomas/mouse. A combination of benzyl isothiocyanate and phenethyl isothiocyanate, given 2 h prior to each gavage of NNK and BaP, was found to be an effective inhibitor of lung tumor formation, reducing the tumor multiplicity to 5.9 +/- 5.7 lung adenomas/mouse (P < 0.001) and completely inhibiting forestomach tumor development. The results of this study provide a convenient model for assessing the efficacy of chemopreventive agents against lung cancer induction by tobacco smoke carcinogens.
-
Comparative Study
Mutagenic activity of gastric fluid from chewers of tobacco with lime.
Although tobacco chewing is strongly associated with a high risk of oral and upper alimentary tract cancers, the nature of mutagenic exposure among users has not been clearly defined. In this study, tobacco-specific and mutagenic exposure of chewers of tobacco with lime was evaluated by analysis of gastric fluid (GF). The pH, nitrite and cotinine levels of GF samples from chewers and non-chewers were determined and the samples were tested for mutagenicity in the Ames Salmonella/microsome assay using Salmonella typhimurium strains TA98, TA100 and TA102. ⋯ While all GF samples from non-chewers were non-mutagenic, samples from chewers were directly mutagenic or upon nitrosation to all the three tester strains and to TA102 strain in the presence of S9. Experiments using scavengers of reactive oxygen species (ROS) showed that mannitol and benzoate abolished the mutagenic response of TA102, indicating that ROS are principally responsible for oxidative damage. The findings provide specific information regarding the mutagenic exposure among tobacco chewers and suggest that tobacco chewing may be an important risk factor in the development of gastric cancer.