Reaction of Fumonisin with Glucose Prevents Promotion of Hepatocarcinogenesis in Female F344/N Rats while Maintaining Normal Hepatic Sphinganine/Sphingosine Ratios
The reaction of th e primar y am ine of fumonisin B1 (FB1) with glucose was hypoth esized to detoxify th is mycotoxin. Eight y 10-day-old fema le F344/N rat s were injected intra peritoneally with dieth ylnitrosam ine (DEN; 15 mg/kg of body weig ht). At 4 wee ks of age, th e wean ed rat s were ran domly assigned to one of four tr eatm ent groups with 20 rat s each. At 9 wee ks of age, four rat s from each tr eatm ent group were kille d. At 12 wee ks, anoth er five rat s from each group were kille d. At 20 wee ks of age, th e rema ining rat s were kille d. In compar ison with th e rat s fed basal diet or FB1-glucose (conta ining 25 pp m of FB1), rat s fed 8 pp m (resid ua l amount of free FB1 in th e FB1- glucose mixtur e) or 25 pp m of FB1 ha d great er alan ine am inotran sfera se activity at 9 an d 20 wee ks of age (P < 0.001), great er endogenous hep at ic prosta glan din E2 production at 20 wee ks of age (P < 0.05), an d significant ly lower plasma cholesterol at 20 wee ks of age (P < 0.01). Placenta l glutath ione S-tran sfera se (PGST )-positive an d γ-glutam yltran sfera se (GGT)-positive altered hepatic foci (AHF) occurr ed only in rat s fed 25 pp m of FB1 at 20 wee ks of age. Hep at ic natura l kille r (NK) cell activities were similar among th e four groups, but th e percenta ge of tota l live r-associat ed mononuclear cells exhibi ting th e NKR-P1bright mark er was significant ly great er in rat s fed FB1- glucose, FB1 (8 pp m) an d FB1 (25 pp m) than in contr ol rat s at 9 wee ks of age, an d FB1-glucose- tr eat ed rat s ha d significant ly lower NKR-P1bright cells as a percenta ge of tota l live r-associat ed mononuclear cells than rat s fed 25 pp m of FB1 at 20 wee ks of age (P < 0.05). PGST- or GGT- positive AHF were not detected in an y tr eatm ent group at 9 or 12 wee ks of age. At 20 wee ks of age, ha lf of th e rat s fed 25 pp m of FB1 ha d PGST- an d GGT-positive AHF . The sp hingan ine (Sa) concentrat ion an d th e Sa/sp hingosine (So) rat io were significant ly great er in th e rat s fed 25 pp m of FB1 diet as compar ed with th e contr ol groups at , respe ctively, 12 or 20 wee ks of age. Therefore, FB -induced hep atotoxicity an d promotion of hep atocarcinogenesis . The Sa/So rat io was not th e most sensitive biomark er of FB1 toxicity.
Reprinted with permission from Journal of Agricultural and Food Chemistry. 49(8): 4113-4121. doi: 10.1021/jf001529i. Copyright 2001 American Chemical Society.