A Study of the Dose Response of Mouse Skin to Cigarette Smoke Condensate

Davies, R F; P, Lee; Rothwell, K.

doi:10.1038/bjc.1974.126

Cited by 11 publications

(3 citation statements)

References 11 publications

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“…As noted in the discussion there are a priori reasons based on the findings of Davies et al (1974) why the linear relationship assumed between log dose and log b (or log WRP) might not hold at the highest dose levels tested. The detailed results of the multiple regression analysis were therefore examined to see where departures from the assumption occurred.…”

Section: Resultsmentioning

confidence: 99%

Fractionation of mouse skin carcinogens in cigarette smoke condensate

P¹,

Rothwell²,

Whitehead³

1977

Br J Cancer

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Summary.-The results of a series of mouse-skin paintings are given for fractions prepared by two schemes designed to concentrate the polycyclic aromatic hydrocarbons (PAH) and their heterocyclic analogues (HETC) present in cigarette smoke condensate into single fractions. It is demonstrated that, for each group, a single index of tumour response, the " Weibull risk parameter " (WRP), can be calculated which, considered in conjunction with two other parameters common to all the groups, adequately describes the pattern of tumour incidence in that group. These indices can be used to calculate for each fraction a further statistic, the " tumorigenic ratio " (TR), which conveniently measures the activity of the fraction relative to wholesmoke condensate on a weight-for-weight basis. From the analyses it is shown that the separation processes can successfully concentrate all types of mouse-skin carcinogenic material, irrespective of the type of condensate used, and that a combination of processes prepares an active concentrate representing 2% by weight of the original condensate.

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Section: Resultsmentioning

confidence: 99%

Fractionation of mouse skin carcinogens in cigarette smoke condensate

P¹,

Rothwell²,

Whitehead³

1977

Br J Cancer

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“…Lee et al (1977) have shown that virtually all the carcinogenic components of whole-smoke condensate are insoluble in water. Davies et al (1974) demonstrated that the use of a hydrophobic alcohol (isopropyl alcohol) as a solvent for condensate increased the incidence of tumours over that achieved with the usual solvents. The present study, using a hydrophilic alcohol, has reduced the incidence.…”

Section: Discussionmentioning

confidence: 99%

“…The doses of condensate used were 189 and 94-5 mg/mouse/week, each alone or with 17.5% or 35% glycerol, the balance being made up from solvent (Table I). These doses were chosen to avoid high-dose suppression and thus to give optimum tumour response (Davies et al, 1974), and to be comparable with glycerol proportions in NSM smoke condensate. Control groups received acetone/glycerol mixtures, or were handled and not otherwise treated (Table I).…”

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confidence: 99%

Effect of glycerol on local and systemic carcinogenicity of topically applied tobacco condensate

Wilson¹,

Clapp²,

Conning³

1978

Br J Cancer

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Summary.-When glycerol was added to tobacco smoke condensate in acetone solvent, the topical carcinogenicity and the ability to produce epithelial hyperplasia in mice was reduced. Two doses of condensate were applied, combined with 2 concentrations of added glycerol. Age-standardized results show that glycerol reduced the incidence of tumours and malignant tumours and of hyperplasia in animals not developing skin tumours. The relative incidences of malignant tumours, benign tumours, hyperplasia and unaffected skin suggest that there is a sequential relationship (i.e. normal skin to hyperplasia to benign neoplasia to malignant neoplasia) which is impeded by glycerol. There was no systemic effect attributable to the condensate.IN STUDIES on the carcinogenicity of smoke condensate of tobacco and NSM* it was noted that NSM condensates showed less than 250% of the tumour-producing activity of tobacco (Clapp et al., 1977). This was attributed to the general reduction of the particulate-phase activity of NSM smoke, but comment was made that the substantial carry-over into smoke of the humectant used (glycerol) might have been a factor of significance. Glycerol constitutes between 40%0 and 50°/ of the particulate phase of NSM smoke and it seemed possible that this amount might influence the response of mouse skin to the carcinogenic effect of smoke condensate, quite apart from any effect of the dilution of carcinogenic constituents. The experiment described here was designed to determine whether the presence ofglycerol, as a diluent of tobacco condensate, itself influenced the carcinogenicity of the condensate irrespective of an effect on dosage.

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Analyses of carcinogenesis dose- response relations with dichotomous data: Implications for carcinogenic risk assessment

Swartz

Riddiough

Epstein

1982

Teratog. Carcinog. Mutagen.

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Dose-response data from experimental and epidemiologic carcinogenicity studies were analyzed in attempts to resolve basic questions in extrapolating from high to low doses and assessing human risk. Four models (Weibull, Mantel-Bryan, Marshall-Groer, and Mancuso-Stewart) were fit to 46 sets of experimental and 4 sets of epidemiologic data by maximizing the likelihood function with a Rosenbrock hill-climbing algorithm. The models were compared as to their adequacy in describing the data and analyzed to determine the effect of carcinogen and breeding category, species, and spontaneous tumor incidence. The shapes of the dose-response curves were analyzed, and errors in risk estimation from linear extrapolation through the origin were calculated. All models were shown to fit the data and to be comparable in accuracy. The dose-response curves were generally "stretched out," particularly for outbred strains, with one or two orders of magnitude of dose increase required to increase the proportion of tumor responders from 10% to 70%. Linear extrapolation through the origin generally underestimated the response at low doses, frequently by several orders of magnitude. The power dependence of tumor incidence on dose was generally found to be of the order of unity, substantially less than assumed in most mathematical models.

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A Study of the Dose Response of Mouse Skin to Cigarette Smoke Condensate

Cited by 11 publications

References 11 publications

Fractionation of mouse skin carcinogens in cigarette smoke condensate

Fractionation of mouse skin carcinogens in cigarette smoke condensate

Effect of glycerol on local and systemic carcinogenicity of topically applied tobacco condensate

Analyses of carcinogenesis dose- response relations with dichotomous data: Implications for carcinogenic risk assessment

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