In mice bearing
Lewis lung carcinoma, rotational and restraint stress specifically increases the formation of lung
metastasis, and restraint stress markedly attenuates the antitumor effects of
cyclophosphamide. The aim of this investigation was therefore to examine the effects of restraint stress on
tumor metastasis in mice bearing MCa mammary
carcinoma, and on the effectiveness of
CCNU and
DTIC. Restraint stress increases MCa mammary
carcinoma metastasis, causes a marked reduction in
cyclophosphamide activity, and a minor attenuation of the effects of
CCNU and
DTIC. The possible occurrence of seasonal factors, observed for the increase by rotational stress of
Lewis lung carcinoma metastasis, was also determined for
cyclophosphamide effectiveness. The survival time of control mice is longer in February than in June, and is not appreciably modified by rotational stress. The effects of
cyclophosphamide are similar in both seasonal periods, and are similarly attenuated by rotational stress. The seasonal effects of rotational stress, and the reduction of the effects of
cyclophosphamide caused by rotational stress, are accompanied by corresponding variations in the number of CD3+ and CD4+ splenic T-lymphocyte subsets and in the CD4+/CD8+ ratio, respectively. The reported effects of stress on
tumor progression and on the effectiveness of
cyclophosphamide thus appear to occur via modulation of immune responses of the host directed against the
tumor. These data appear of interest for their experimental implications, and suggest the opportunity to consider the role that the stress during treatment may play in determining the effectiveness of clinical antitumor
chemotherapy.