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

Abstract

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.

Evaluation of the Genotoxic and Cytotoxic Potential of Mainstream Whole Smoke and Smoke Condensate from a Cigarette Containing a Novel Carbon Filter

“…For detecting the bacterial mutagens in cigarette smoke, the mutagenicity of mainstream CSC was evaluated in Salmonella typhimurium strain TA98 with S9 metabolic activation, the most sensitive strain and condition (Doolittle et al, 1990). The results are shown in Table 2 with data expressed as both revertants per milligram of tar and revertants per cigarette.…”

“…Smoke from the six cigarettes was tested in the SCE assay without S9 metabolic activation since in contrast to the Ames test, SCE assays without S9 metabolic activation are reported to be more sensitive to cigarette smoke-related chemicals than SCE assays with S9 activation (Bombick et al, 1995b; Doolittle et al, 1990). Figure 1 depicts the induction of SCEs/cell with increasing concentration of CSC from the six cigarettes (expressed as fig tar/ml) without an S9 metabolic activation mixture.…”

“…Genotoxic potential of the tobacco smoke was measured by the Ames bacterial mutagenicity assay and the mammalian sister chromatid exchange assay. Both of these assays have been used to measure the genotoxic potential of cigarette smoke (Doolittle et al, 1990). The neutral red assay was utilized to measure the cytotoxic potential of cigarette smoke in this study.…”

“…The in vitro toxicological assessment consisted of measures of both genotoxicity (sister chromatid exchange and bacterial mutagenicity assays) and cytotoxicity (neutral red assay). These particular assays have been previously used to assess the genotoxic and cytotoxic potential of cigarette smoke (Bombick et al, in press;Doolittle et al, 1990). Past studies investigating the toxicity of cigarette smoke mostly have used exposures to the particulate phase of cigarette smoke (cigarette smoke condensate).…”

Will chronic e-cigarette use cause lung disease?

“…However, chronic inflammation can act as a precursor to cancer, and continued influx of neutrophils, with the subsequent increase in free elastase levels, can lead to cell damage and denudation of the epithelia (22,143). Tobacco exposure is also associated with cellular cytotoxicity, including increased apoptosis, autophagosome formation, membrane permeability, and mitochondrial damage (46,78,87,129). Furthermore, micronuclei form when chromosomes or parts of chromosomes are excluded from daughter nuclei following cell division (56).…”