The effect of step-down heating on mouse small intestinal mucosa.

Step-down heating (SDH) was investigated in mouse small intestine by giving a primary (conditioning) treatment at or above 43 degrees C followed by a test treatment below 43 degrees C. Crypt dose-response curves following SDH were compared with those obtained using the test treatment alone; the SDH effect was characterized by a reduction in shoulder (an additive effect) and an increase in slope (thermosensitization). The thermosensitization ratio, defined as slope SDH-heated/slope single-heated, was independent of the conditioning temperature but increased to a maximum of approximately three as the duration of conditioning increased. Thermosensitization was eliminated when the conditioning treatment was itself sufficient to cause significant crypt loss and, also, when the interval between the two treatments was 0.5 h or longer. This period was less than that required for either recovery of the 'shoulder' on the crypt dose-response curve or the development of thermotolerance following the primary treatment. Thermotolerance which develops in intestine during prolonged hyperthermia (after approximately 100 min) was not affected by SDH and Arrhenius analysis indicated that the activation energy for temperatures below 43 degrees C was not significantly altered by SDH. In summary, the SDH effect on small intestine, assessed using the crypt loss endpoint, was similar to thermosensitization observed in vitro. However, the lower magnitude of the effect and its complex dependence on the primary heat treatment suggest either that crypt cells respond to SDH in a unique and characteristic manner or that the crypt assay in vivo and reproductive survival in vitro do not reflect the same endpoint.