Dietary fat modulates immunoresponsiveness in UV-irradiated mice.
Previous studies have shown that a high level of dietary lipid (corn oil) exacerbates UV-carcinogenic expression in hairless mice. Furthermore, it was demonstrated that this effect occurs at the postinitiation, or promotion, stage of UV-carcinogenesis--a stage believed to be modulated immunologically. Thus, we sought to examine the influence of dietary lipid on specific immune parameters at various times within a UV-carcinogenic protocol, with the purpose of detecting potential relationships to UV carcinogenesis. Hairless mice were fed either a high- (12%, wt/wt, corn oil) or low-fat (0.75%, wt/wt, corn oil) diet for 2 weeks prior to start of the UV or experimental protocols. Animals were sensitized to dinitrochlorobenzene (DNCB) hapten and delayed-type hypersensitivity (DTH) was assessed. Delayed-type hypersensitivity was significantly suppressed (P = 0.01) in the high-fat group, even before UV irradiation. Although both groups exhibited UV-induced suppression of this response, the high-fat group was totally suppressed after 3 weeks of UV, whereas the low-fat group exhibited reactivity through week 8. The splenic T-lymphocyte (Thy 1.2+) population had declined by about 50% at the time of UV termination (11 weeks). Dietary lipid exerted no apparent influence upon this T-cell population. However, after 6 weeks of UV, I-J+ cells (a marker shown to be acquired adaptively by suppressor T lymphocytes) began to increase. By week 15 (4 weeks post-UV) I-J+ cells had increased by about 65% in the high-fat group, twice the % increase that occurred in the low-fat group. When UV-induced tumors were transplanted to recipient animals receiving various periods (0, 6, 11 weeks) of UV irradiation, no significant differences in median tumor rejection times between the two dietary groups occurred at 0 or 6 weeks. After 11 weeks of UV, the low-fat group exhibited a tumor rejection time that was comparable to that of nonirradiated animals, i.e. 21 days. However, median tumor rejection time for the high-fat group was greater than 63 days, significantly (P = 0.01) longer than that of the low-fat group. Thus, suppression of tumor rejection by high fat occurred at a time when high fat had been shown to exacerbate carcinogenic expression and when I-J+ cells had markedly increased. These data demonstrate that level of dietary lipid modulates immunoresponsiveness in UV-irradiated animals and is compatible with the thesis that immune suppression may account for the exacerbation of carcinogenic expression elicited by high dietary fat.
Black
H S
HS
Veterans Affairs Medical Center, Houston, TX 77030, USA.
Okotie-Eboh
G
G
Gerguis
J
J
Urban
J I
JI
Thornby
J I
JI
D000818:Animals; D003043:Cocarcinogenesis; D004041:Dietary Fats / Q000633:toxicity*; D005260:Female; D007108:Immune Tolerance / Q000528:radiation effects*; D051379:Mice; D008812:Mice, Hairless; D009374:Neoplasms, Experimental / Q000209:etiology / Q000276:immunology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004041:Dietary Fats