Immunobiology of lipid-modulated UV-carcinogenesis.
Previous studies have demonstrated that high levels of dietary fat exacerbate UV-carcinogenic expression and suppress immunoresponsiveness. The latter may account for the former response. We have explored this possibility through T-lymphocyte transfer studies. Groups of HRA.HRII-c/+/Skh hairless mice were fed isocaloric diets containing high (12%, wt./wt.) or low (0.75%) levels of corn oil and irradiated 5 days/week (1.0 J cm-2/day) for 11 weeks with filtered FS-40 sunlamps. At weeks nine and 12, enriched T-cells from high-fat donors that had received 11 weeks of UV were transferred intravenously to low-fat recipients. Median tumor times for high-fat, low-fat recipient, and low-fat groups were 15.8, 18.5, and 21.6 weeks, respectively. The significantly (P < 0.03) shortened primary tumor latent period in low-fat-fed animals resulting from transfer of relatively low levels of T-cells derived from chronically irradiated high-fat donors demonstrates that the influence of dietary fat upon UV-carcinogenic expression is, at least partially, mediated via immunologic mechanisms. Further studies suggest that fat-modulated carcinogenesis can, itself, be regulated immunologically. A soluble T-14 (mouse squamous carcinoma cell line) cell-free fraction was injected subcutaneously at axillae and inguen of animals fed the high-fat diet during the first three weeks of UV or immediately post-UV. At week four post-UV, animals were challenged with T-14 cells injected subcutaneously at both flanks. 21 days post-challenge the tumor volumes of low-fat and high-fat immunized animals were zero versus 593 mm3 for the high-fat group (P < 0.007). Such treatment significantly (P < 0.03) increases the latent period of UV-induced primary tumors as well, when compared to non-treated high-fat-fed animals.
Veterans Affairs Medical Center, Houston, TX, USA. hblack@bcm.tmc.edu
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D019264:Adoptive Transfer; D000818:Animals; D015197:Carcinogenicity Tests; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D004041:Dietary Fats / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D014466:Ultraviolet Rays
D004041:Dietary Fats