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Temporal Factors Alter Effects of Social Housing Conditions on Responses to Chemotherapy and Hormone Levels in a Shionogi Mammary Tumor Model

From the Departments of Psychology and Biology, Trent University, Peterborough, Ontario, Canada (L.R.K.); the Department of Kinesiology, University College of the Fraser Valley (H.N.A., K.S.S.), Abbotsford, British Columbia, Canada; and the Department of Cellular & Physiological Sciences, Faculty of Medicine, University of British Columbia (J.T.E., J.W.), Vancouver, British Columbia, Canada.

Address correspondence and reprint requests to Leslie R. Kerr, PhD, Departments of Psychology and Biology, Trent University, 1600 West Bank Drive, Peterborough, Ontario, K9J 7B8 Canada. E-mail: lkerr{at}trentu.ca

Objective: To identify possible hormonal factors involved in the differential responses to chemotherapy observed in our tumor model, we investigated if the timing among tumor cell injection, rehousing, and chemotherapy administration differentially affects levels of corticosterone (CORT), growth hormone (GH), and testosterone and tumor and host responses to chemotherapy.

Methods: Mice were reared either individually (I) or in groups (G). At 2 to 4 months, mice were injected with tumor cells and retained in their original housing conditions or rehoused into different experimental groups (GG, IG, II, GI) either immediately (experiment 1) or 14 days later (experiment 2); chemotherapy was administered when tumors weighed approximately 0.8 g.

Results: In experiment 1, IG and GG mice had better responses to chemotherapy than GI mice. Chemotherapy increased CORT levels in II mice and decreased GH levels in GI mice compared with those of their drug vehicle-treated counterparts. Under the temporal conditions of experiment 2, IG and GG mice lost the advantage seen in experiment 1 in terms of tumor and host responses to chemotherapy. Before chemotherapy administration, CORT levels in IG mice and GH levels in GI mice were higher than those in mice in all other housing conditions. At 1 day after chemotherapy, CORT levels were higher for chemotherapy-treated than for drug vehicle-treated IG mice, and at 5 days post chemotherapy, GH levels were higher in GI than in IG mice.

Conclusions: Temporal relationships among tumor cell injection, rehousing, and chemotherapy administration critically influence responses to chemotherapy; these effects may be mediated, in part, by alterations in hormone levels.

Key Words: housing • chemotherapy • hormones • temporal interactions • Shionogi carcinoma

Abbreviations: GG = from group to group housing; II = from individual to individual housing; IG = from individual to group housing; GI = from group to individual housing; CORT = corticosterone; GH = growth hormone; T = testosterone; AD = Adriamycin; CY = cyclophosphamide; TGD = tumor growth delay; SC115 = Shionogi carcinoma 115; C = tumor cell-injected, chemotherapy-treated mice; V = tumor cell- injected, drug vehicle-treated mice.