Inhibition of metabolic cooperation by cigarette smoke condensate and its fractions in V-79 Chinese hamster lung fibroblasts.

Abstract

This study was performed to determine the usefulness of the intercellular metabolic cooperation assay for analysis of a complex mixture and to compare the results obtained with previously conducted in vivo tumor promoter assays. One hundred 2R1 cigarettes were smoked according to Federal Trade Commission guidelines and the resulting condensate was separated into a water/methanol-soluble fraction (which was further partitioned into acidic and basic components) and an organic solvent-soluble fraction (which was then chromatographed on silicic acid with petroleum ether, benzene/petroleum ether, benzene, ether, and methanol). The following fractions were positive in the metabolic cooperation assay (in decreasing order of activity): organic solvent-soluble, acidic, whole condensate, and water/methanol-soluble fractions as well as the ether, benzene, and benzene/petroleum ether eluates. The basic fraction and the petroleum ether and methanol eluates were negative. In general, the metabolic cooperation assay results were comparable to previously published results obtained on mouse skin.Epidemiological investigations have convincingly established the link between tobacco smoking and lung cancer. The 1962 Royal College of Physicians report (1) and numerous reports from the U.S. Surgeon General (2) and the U.S. Public Health Service (3) have shown this relationship to be unequivocal. Furthermore, the experimental induction of benign and malignant neoplasms by the particulate phase of tobacco smoke (tobacco tars) has been accomplished in hamsters, mice, rats, rabbits, and dogs (4,5). It must be noted, however, that the experimental induction of bronchogenic carcinoma in these animals has rarely been demonstrated (5) and no reliable, welldefined, animal model for the induction of lung cancer exists at present.Short-term cell-mediated bacterial mutagenicity (6) and mammalian cell-transformation assays (7) conducted with tobacco tars and subfractions have shown considerable mutagenic and transforming activity. However, it has been noted that the concentration of mutagens alone in tar cannot account adequately for its observed tumorigenicity (4,8). Consistent with the two-stage theory of carcinogenesis, which evolved from the original observations by Rous and Kidd (9), Berenblum (10, 11), Mottram (12), and, later, Boutwell (13,14), it is evident that tobacco tars are complete carcinogens-containing both initiating and promoting elements. Such a conclusion is supported epidemiologically by the decreased lung cancer risk noted in persons who have stopped smoking (4, 15) (an observation consistent with the known reversibility of the tumor promotion phase of tumorigenesis) and experimentally by the presence of tumor promoters and cocarcinogens in tobacco tars and fractions demonstrated by using classical mouse skin painting assays (4,16 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely t...

Inhibition of metabolic cooperation in Chinese hamster V79 cells by various organic solvents and simple compounds

“…If, as has been shown with many known teratogens, tumor promoters and reproductive toxicants (see reviews Trosko and Chang, 1984;also Aylsworth et al, 1984;Rubinstein et al, 1984;Hartman and Rosen, 1983;Malcolm and Mills, 1984;Welsch and Stedman, 1984), inhibition of gap junction-mediated intercellular communication contributes in part to teratogenesis, tumor promotion and reproductive dysfunction, then the results of this study have several implications.…”

Electronic cigarette liquids impair metabolic cooperation and alter proteomic profiles in V79 cells

“…∞: when dividing integer with 0 as in the case when expressing ratio where XIC value of control modified peptide is 0 On the other hand, we found that both liquids negatively affected metabolic cooperation as assessed by metabolic HPRT assay, indicating impaired intercellular communication between wild type and HPRT deficient cells. The metabolic cooperation assay has been historically used to study gap junctional intercellular communication as it requires cell-to-cell contact and has also shown a level of correlation with carcinogenesis [54][55][56][57]. Cigarette smoke condensate has been previously shown to disrupt metabolic cooperation in V79 cells [55], but so far there were no reports on using this assay for studying e-cigarettes.…”

“…The metabolic cooperation assay has been historically used to study gap junctional intercellular communication as it requires cell-to-cell contact and has also shown a level of correlation with carcinogenesis [54][55][56][57]. Cigarette smoke condensate has been previously shown to disrupt metabolic cooperation in V79 cells [55], but so far there were no reports on using this assay for studying e-cigarettes. Biological consequences of impaired intercellular communication are broad and this effect of e-cigarettes remains to be studied in detail.…”

Commentary: Is the concept of “tumor promotion” a useful paradigm?

“…One likely explanation is that the chemicals in cigarette smoke act more as tumor promoters by selecting preexisting mutated p53±containing cells (the``initiated'' cells). Several years ago, chemicals from cigarette smoke were shown to inhibit gapjunctional intercellular communication (GJIC), a proposed cellular mechanism in tumor promotion [32].…”