title: Modulation of natural killer activity by 12-O-tetradecanoylphorbol-13-acetate and benzoyl peroxide in phorbol ester-sensitive (SENCAR) and resistant (B6C3F1) mice.
abstract: Following two weeks of topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) at 2, 4 and 8 micrograms/mouse on alternate days (7X total) or benzoyl peroxide (BZP) at 10, 20 and 40 mg/mouse, natural killer (NK) activity was determined in local (lymph nodes draining the lower dorsal region) and systemic (spleen) lymphoid tissue in phorbol ester-sensitive (SENCAR) and resistant (B6C3F1) mice. SENCAR mice, sensitive to tumor induction by TPA in two-stage chemical-induced carcinogenesis protocols, demonstrated suppression of NK activity in the spleen (no significant change in lymph nodes) and substantial dose-dependent increases in cell numbers in these organs after topical exposure to TPA. B6C3F1 (C57BL/6 X C3H F1) mice, reported to be resistant to TPA-induced promotion, demonstrated significant increases in NK activity in lymph nodes/spleen with an increase in cell numbers in the draining nodes only. Unlike the C57BL/6 parental strain, B6C3F1 mice are also reported to be resistant to promotion with BZP. Significantly, studies in this laboratory indicated that B6C3F1 mice dosed with BZP demonstrated increased NK activity in the spleen as was observed after dosing with TPA. These data suggest that alterations in NK activity as a result of exposure to tumor promoters may, in part, account for the resistance of particular strains of mice to tumor development. In both SENCAR and B6C3F1 mice, the blastogenic response of spleen cell suspensions isolated from TPA-dosed animals to phytohemagglutinin (PHA), a T cell lectin, was suppressed in a dose-dependent manner; BZP had no effect on spleen cell responses in either strain. Blastogenic responses of lymph node cells to PHA were enhanced in both strains of mice after topical application of TPA and BZP. Therefore, alterations in lymphoid cell responsiveness to PHA appeared unrelated to the reported sensitivities of SENCAR and B6C3F1 mice to tumor promotion.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
authors.forename: L W
authors.initials: LW
authors.lastname: Updyke
authors.forename: A
authors.initials: A
authors.lastname: Chuthaputti
authors.forename: R W
authors.initials: RW
authors.lastname: Pfeifer
authors.forename: G K
authors.initials: GK
authors.lastname: Yim
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001585:Benzoyl Peroxide / Q000494:pharmacology*; D004351:Drug Resistance; D007113:Immunity, Innate / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D010545:Peroxides / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D010545:Peroxides; D010835:Phytohemagglutinins; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide