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At least 343 records · Page 19Linked to original sources
PubMed1990

Comparative studies on the genotoxic activity of mainstream smoke condensate from cigarettes which burn or only heat tobacco.

The in vitro genotoxic activity of mainstream cigarette smoke condensate (CSC) from cigarettes which heat but do not burn tobacco was compared to that of CSC from cigarettes which burn tobacco. CSCs from five cigarettes were compared. Three of the cigarettes [the Kentucky reference research cigarette (1R4F), a commercially available ultra-low tar brand (ULT) and a commercially available ultra-low tar menthol brand (ULT-menthol]) burn tobacco while two of the cigarettes [a regular (TEST) and a menthol (TEST-menthol]) heat tobacco. CSC from all cigarettes were collected by identical standard techniques, which involved collecting mainstream smoke particulate matter on Cambridge filter pads under FTC smoking conditions. The pads were extracted with DMSO, and the CSCs obtained [10 mg total particulate matter (TPM)/ml DMSO] were evaluated at identical concentrations in an in vitro genetic toxicology test battery. CSCs from 1R4F, ULT, and ULT-menthol cigarettes were mutagenic in Ames bacterial strains TA98, TA100, TA1537, and TA1538 in the presence of metabolic activation (S9 from Aroclor-induced rat liver) but negative in strain TA1535. In the absence of metabolic activation, 1R4F, ULT, and ULT-menthol CSCs were not mutagenic except for a weak response in strain TA1537 for the 1R4F and ULT CSCs. TEST and TEST-menthol CSCs were nonmutagenic in all five bacterial strains, both with and without metabolic activation. CSCs from 1R4F, ULT, and ULT-menthol cigarettes were positive in the CHO-chromosomal aberration assay and in the CHO--sister chromatid exchange assay both with and without metabolic activation while TEST and TEST-menthol CSCs were negative in both assays, either with or without metabolic activation. CSCs from 1R4F, ULT, and ULT-menthol cigarettes were weakly positive in inducing DNA repair in cultured rat hepatocytes while TEST and TEST-menthol CSCs were negative in this assay. All five CSCs were nonmutagenic in the CHO-HGPRT assay both with and without metabolic activation. CSCs from the 1R4F, ULT, and ULT-menthol cigarettes were cytotoxic in the CHO-HGPRT assay, both with and without metabolic activation, while TEST and TEST-menthol CSCs were not cytotoxic under either condition. These results demonstrate that mainstream CSCs from the TEST and TEST-menthol cigarettes are neither genotoxic nor cytotoxic under conditions where CSCs from 1R4F, ULT, and ULT-menthol cigarettes are genotoxic and/or cytotoxic in a concentration-dependent manner.

Animals↗
PubMed1990

Genetic toxicology studies comparing the activity of sidestream smoke from cigarettes which burn or only heat tobacco.

The results of in vitro genetic toxicology studies of sidestream cigarette smoke (SSCS) from cigarettes which heat but do not burn tobacco were compared to those of sidestream smoke from cigarettes which burn tobacco. SSCSs from 5 cigarettes were compared. Three of the cigarettes, the Kentucky reference research cigarette (1R4F), a commercially available ultra-low-tar brand (ULT) and a commercially available ultra-low-tar menthol brand (ULT-menthol) burn tobacco while two of the cigarettes, a regular (TEST) and a menthol (TEST-menthol) heat tobacco. SSCSs from all cigarettes were prepared by identical techniques, which involved collecting sidestream smoke particulate matter on Cambridge filter pads and combining the particulate matter with the vapor-phase materials collected by bubbling the smoke exiting the Cambridge pad through DMSO. The SSCSs obtained (equivalent to 0.4 cigarettes/ml DMSO) were evaluated at identical concentrations in an in vitro genetic toxicology test battery. SSCS from 1R4F, ULT and ULT-menthol cigarettes produced positive results in Ames bacterial strains TA98, TA100, TA1537 and TA1538 in the presence of metabolic activation (S9 from Aroclor-induced rat liver) but negative results in strain TA1535. In the absence of metabolic activation, 1R4F, ULT and ULT-menthol SSCSs were not significantly mutagenic. TEST and TEST-menthol SSCSs produced negative results in all 5 bacterial strains, both with and without metabolic activation. SSCS from 1R4F, ULT and ULT-menthol cigarettes produced positive results in the CHO chromosomal aberration assay and in the CHO sister-chromatid exchange assay both with and without metabolic activation while TEST and TEST-menthol SSCSs produced negative results in both assays, either with or without metabolic activation. The SSCSs from 1R4F, ULT and ULT-menthol cigarettes were weakly positive in inducing DNA repair in cultured rat hepatocytes while TEST and TEST-menthol SSCSs were negative in this assay. All 5 SSCSs were nonmutagenic in the CHO-HGPRT assay both with and without metabolic activation. SSCSs from the 1R4F, ULT and ULT-menthol cigarettes were cytotoxic in the CHO-HGPRT assay, both with and without metabolic activation, while TEST and TEST-menthol SSCSs were not cytotoxic under either condition. These results demonstrate that sidestream smoke from cigarettes which heat but do not burn tobacco (TEST and TEST-menthol) was neither genotoxic nor cytotoxic under conditions where sidestream smoke from cigarettes which burn tobacco (1R4F, ULT and ULT-menthol) was genotoxic and/or cytotoxic in a concentration-dependent manner.

Animals↗
PubMed2004

Extinguishing the rewarding value of smoke cues: pharmacological and behavioral treatments.

The present study examined several pharmacological and behavioral treatments designed to promote extinction of the responses to rewarding cigarette smoke cues. Pharmacological treatments comprised nicotine skin patches (21 mg/24 hr) and the nicotinic acetylcholine receptor antagonist mecamylamine (10 mg/day), administered separately or in combination. Behavioral manipulations included switching to denicotinized cigarettes, to cigarettes having different menthol flavor, or to ventilated-filter (low tar and nicotine) cigarettes. Smokers were assigned to the various treatments for 2 weeks before they quit smoking. During weekly test sessions, subjects rated the rewarding effects of their usual brands of cigarettes or cigarettes with different menthol content (mentholated vs. nonmentholated). Over the 2-week treatment period, all pharmacological treatments reduced ratings of reward for the usual-brand test cigarettes. Switching to smoking denicotinized cigarettes for 2 weeks similarly decreased rewarding effects of the usual-brand test cigarettes. Subjects also strongly preferred cigarettes with the same menthol content to which they were accustomed. However, manipulating the menthol content of the cigarettes smoked during the 2 weeks of treatment had different effects, depending on whether smokers habitually smoked mentholated or nonmentholated cigarettes. For menthol smokers, removal of the menthol cue hampered extinction of reward ratings for the usual-brand (mentholated) test cigarette. For nonmenthol smokers, addition of the menthol cue did not affect the progress of extinction of nonmenthol smoke cues. These findings demonstrate the importance of sensory cues in determining subjective reward and show that the reward value of these cues can be altered by removal of nicotine from tobacco or by pharmacological manipulations that interfere with the reinforcing effects of nicotine.

Administration, Cutaneous↗
PubMed2006

Chemical and cold sensitivity of two distinct populations of TRPM8-expressing somatosensory neurons.

The cold- and menthol-sensing TRPM8 receptor has been proposed to have both nonnociceptive and nociceptive functions. However, one puzzle is how this single type of receptor may be used by somatosensory neurons to code for two distinct sensory modalities. Using acutely dissociated rat dorsal root ganglion (DRG) neurons without culture, we show that TRPM8 receptors are expressed on two distinct classes of somatosensory neurons. One class is sensitive to menthol and features nonnociceptive neuron properties, including capsaicin-insensitive, ATP-insensitive, transient acid response, and expression of TTX-sensitive sodium channels only. This class is termed the menthol-sensitive/capsaicin-insensitive neuron class (MS/CIS). The other class is also sensitive to menthol but has characteristics of nociceptive neurons including capsaicin-sensitive, ATP-sensitive, prolonged acid response, and expression of both TTX-sensitive and TTX-resistant sodium channels. This class is termed the menthol-sensitive/capsaicin-sensitive neuron class (MS/CS). The presence of these two neuron classes in acutely dissociated DRG neurons support the idea that TRPM8 receptors can have both nonnociceptive and nociceptive functions. While both neuron classes respond to menthol and cold, the overall responses induced by menthol and cold are significantly larger in MS/CIS than in MS/CS neurons. Furthermore, low concentrations of menthol produce strong selection of the MS/CIS neuron population over the MS/CS neuron population. On the other hand, the population selection becomes weaker with higher concentrations of menthol. TRPM8 current density shows significant higher in MS/CIS neurons than in MS/CS neurons, suggesting different expression levels of TRPM8 receptors between the two neuron populations, and this difference may provide a mean of selective activation of MS/CIS neurons at low stimulation intensity.

Animals↗