title: Comparison of dermal tumor promotion activity of cigarette smoke condensate from prototype (heated) cigarette and reference (combusted) cigarette in SENCAR mice.
abstract: Test cigarette (prototype "heated" cigarette) was evaluated on its dermal tumor promotion activity in SENCAR mice relative to conventional 3R4F cigarette. Mainstream cigarette smoke was generated under the modified Health Canada Intensive Regimen, and smoke condensate (CSCs) were collected using cold traps and extracted with acetone. Female mice received a topical application of 7,12-dimehtylbenz(a)anthracene (DMBA) as the tumor initiator on the back skin during Week 1. Subsequently, CSC was repeatedly applied as the tumor promoter at 5 doses, up to 30 mg tar/application, three times per week for 30 weeks. Test groups showed a clearly longer latency at lower doses (⩽15 mg), but the difference was less clear at higher doses (⩾22.5 mg), while mortalities were not affected throughout the study. Test groups also had consistently lower incidence and multiplicity of neoplasms, as well as lower incidences of non-neoplastic changes (e.g., inflammations and squamous epithelial hyperplasia on the site of application). The group without DMBA initiation did not induce any neoplasm but the respective Reference group showed an increase in tumorigenicity. In conclusion, the study demonstrated significant reduction in dermal irritancy and tumorigenicity of Test CSC compared to Reference CSC.
authors.affiliation: Product Science Division, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, Japan. Electronic address: hiroyuki.tsuji@jt.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuji
authors.affiliation: Scientific and Regulatory Division, Japan Tobacco Inc., 2-2-1. Toranomin, Minato-ku, Tokyo, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Okubo
authors.affiliation: Scientific and Regulatory Division, Japan Tobacco Inc., 2-2-1. Toranomin, Minato-ku, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujimoto
authors.affiliation: Product Science Division, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fukuda
authors.affiliation: Product Science Division, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Scientific and Regulatory Affairs, JT International S.A. 1, rue de la Gabelle, 1211 Geneva, Switzerland.
authors.forename: K Monica
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Product Science Division, R&D Group, Japan Tobacco Inc., 6-2, Umegaoka, Aoba-ku, Yokohama, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshimura
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity; D000279:Administration, Cutaneous; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D009929:Organ Size / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D062789:Tobacco Products / Q000009:adverse effects* / Q000032:analysis
chemical_list: D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene
keywords: Cigarette smoke condensate; Dermal tumor; Heated cigarette; Tumor promotion; Tumorigenicity