2-オクチル-1-シクロプロペン-1-オクタン酸

THE ROLE OF DIET & NUTRITION IN MODIFYING TUMOR INDUCTION BY CHEMICAL CARCINOGENS IN FOODS & FEEDS IS REVIEWED. FOOD CONTAMINANTS OF MAJOR CONCERN INCLUDE STERCULIC ACID & MALVALIC ACID.[PETERING HG; DIET, NUTRITION, AND CANCER; ADV EXP MED BIOL 91: 207 (1977)]

AFLATOXIN Q1 (AFQ), A BIOTRANSFORMATION METABOLITE OF AFLATOXIN B1 (AFB), IS FORMED IN VITRO BY HUMAN & MONKEY LIVER MICROSOMES. AFQ WAS FED TO DUPLICATE LOTS OF 80 RAINBOW TROUT FINGERLINGS @ 100 PPB IN A SEMI-PURIFIED TEST DIET FOR 10 MONTHS. ADDNL LOTS WERE FED 100 PPB AFQ PLUS 50 PPM STERCULIC ACID, & 50 PPM CYCLOPROPENE FATTY ACID (CPFA), 4 PPB AFB & THE BASAL TEST DIET TO SERVE AS CONTROLS. HEPATOCELLULAR CARCINOMA INCIDENCES @ 12 MONTHS WERE AS FOLLOWS: 100 PPB AFQ- 12/114 (10.6%); 4 PPB AFB- 55/114 (48.2%); 50 PPM CPFA- 44/107 (41.1%); 100 PPB AFQ PLUS 50 PPM CPFA (STERCULIC ACID)- 106/119 (89.1%) & CONTROL 0/120 (0%). RESULTS ESTABLISH THE CARCINOGENICITY OF AFQ TO RAINBOW TROUT, THE SYNERGISTIC INTERACTION BETWEEN AFQ & CPFA & INDICATE THAT AFQ IS A POTENT LIVER CARCINOGEN ABOUT 100 TIMES LESS CARCINOGENIC THAN AFB.

RAINBOW TROUT FED A DIET CONTAINING 20 UG OCHRATOXIN A PER KG OF DIET, TOGETHER WITH STERCULIC ACID, DEVELOPED HEPATOMAS (NUMBER UNSPECIFIED). NO TUMORS WERE OBSERVED WHEN OCHRATOXIN A WAS FED ALONE AT CONCN OF 16, 32, OR 64 UG/KG OF DIET FOR 8 MONTHS.

RAINBOW TROUT FED A DIET CONTAINING 200 PPM OF STERCULIC ACID & MALVALIC ACID, SUBSTANCES THAT GREATLY INCR THE SENSITIVITY OF TROUT LIVER CELLS TO CARCINOGENIC EFFECTS OF AFLATOXIN B1. AFTER 4 WK, PECULIAR CLEFT-LIKE STRIATIONS APPEARED IN CYTOPLASM OF HEPATOCYTES. THESE ALTERATIONS BECAME PROGRESSIVELY MORE FREQUENT & MARKED WITH CONTINUED FEEDING OF DIET. AT 8 & 12 WK, ROUGH-SURFACED ENDOPLASMIC RETICULUM CONTAINED MANY PARALLEL ARRAYS & WHORLED PROFILES OF MEMBRANE MATERIAL. GLUCOSE-6-PHOSPHATASE ACTIVITY IN LIVER WAS SIGNIFICANTLY DECREASED.

IN MALE WEANLING RATS FED BASAL DIETS OF SATURATED OR UNSATURATED FAT, THE FOLLOWING ADDITIONS WERE MADE: BASAL DIET; AFLATOXIN B1 @ 1.7 PPM; STERCULIC ACID @ 210 PPM; & AFLATOXIN B1 @ 1.7 PPM, PLUS STERCULIC ACID @ 210 PPM. RATS CONSUMED THESE DIETS FOR 2 MONTHS & THEREAFTER WERE FED UNSUPPLEMENTED BASAL DIET UNTIL SACRIFICE 9 MONTHS LATER. GROWTH WAS DEPRESSED IN ALL RATS GIVEN DIETARY SUPPLEMENTS BUT NO SYNERGISTIC INHIBITION WAS OBSERVED, REGARDLESS OF FAT SOURCE. LIVER WEIGHT DOUBLED IN RESPONSE TO AFLATOXIN; HOWEVER, ONLY WHEN DIET CONTAINED UNSATURATED FAT DID STERCULIC ACID, IN COMBINATION WITH AFLATOXIN, EXAGGERATE THE INCREASE IN LIVER WEIGHT. IN RATS FED SATURATED FAT DIET, AFLATOXIN ADMIN TO RATS FED THE CONTROL OR STERCULIC ACID SUPPLEMENT DIETS RESULTED IN MARKED INCREASE IN PLASMA CHOLESTEROL LEVELS; THE UNSATURATED FAT DIETS, SUPPLEMENTED WITH AFLATOXIN, EVOKED A SLIGHT INCREASE IN PLASMA CHOLESTEROL CONTENT WHICH WAS NULLIFIED BY STERCULIC ACID SUPPLEMENTATION.

CYCLOPROPENOID FATTY ACIDS IN STERCULIA FOETIDA OIL AT DOSE LEVEL OF 200 PPM WERE FED TO FINGERLING RAINBOW TROUT FOR 4 WK, & 500 PPM WAS FED TO RATS FOR 2- & 4 WK PERIODS. LIVERS OF ALL ANIMALS WERE LARGE & MODERATELY FATTY; LIVER WEIGHT, CONTENT OF HEPATIC DNA, MITOTIC INDEX, & INCORPORATION OF (3)H-THYMIDINE INTO NUCLEAR DNA OF HEPATOCYTES WERE INCREASED SIGNIFICANTLY ABOVE THOSE OF CONTROL ANIMALS. HISTOLOGIC & CYTOLOGIC ALTERATIONS (FOAMY CYTOPLASM WITH NUMEROUS FAT DROPLETS, LARGE & HYPERCHROMATIC NUCLEI, ENLARGED & SOMETIMES MULTIPLE NUCLEOLI, & FREQUENT MITOSIS) WERE EVIDENT AFTER 2 WK OF CYCLOPROPENOID FATTY ACID FEEDING & VERY SIMILIAR IN BOTH SPECIES.

STERCULIC ACID IS A NATURALLY OCCURRING CYCLOPROPENOID FATTY ACID. THE DISTRIBUTION OF RADIOACTIVITY FROM STERCULIC ACID, LABELED ON 9,10-METHYLENE C OF THE CYCLOPROPENE RING, WAS INVESTIGATED IN TROUT, S GAIRDNERI. OF THE ADMIN DOSE, 50% WAS EXCRETED IN FECES & URINE BY 168 HR, BUT LESS THAN 1% OF THE DOSE WAS EXPIRED AS CO2 DURING THE SAME TIME PERIOD. INCORPORATION OF RADIOACTIVITY INTO MOST ORGANS PEAKED AT 119 HR & THE MAJORITY OF THE LABEL IN THE LIVER WAS IN THE FATTY ACID PORTION OF THE LIPID FRACTION. RAINBOW TROUT READILY ABSORB, TRANSPORT & INCORPORATE STERCULIC ACID INTO TISSUE LIPID, INCL MEMBRANE LIPID, BUT CANNOT OXIDIZE THE METHYLENE C OF THE CYCLOPROPENOID TO CO2.

CYCLOPROPENOID FATTY ACIDS (CPFA), NATURALLY PRESENT IN COTTONSEED OIL, ARE CARCINOGENS & EXHIBIT A POTENT SYNERGISTIC EFFECT ON AFLATOXIN B1 HEPATOCARCINOGENESIS IN RAINBOW TROUT. THE PREDOMINANT CPFA CONSTITUENTS OF COTTONSEED OIL ARE MALVALIC & STERCULIC ACID.

MALAYSIAN KAPOK (C PENTANDRA) SEEDS CONTAIN ABOUT 28% OIL. THE OIL FROM BOTH RAW & ROASTED SEEDS PRODUCED A POSITIVE HALPHEN TEST FOR CYCLOPROPENOID FATTY ACIDS. ACID VALUE, FATTY ACID COMPOSITION BY GLC, I VALUE, REFRACTIVE INDEX, SAPONIFICATION NUMBER, & UNSAPONIFIABLES OF THE OIL WERE ALSO DETERMINED. THE VALUES (AREA %) FOR FATTY ACIDS AS METHYL ESTERS WERE: MALVALIC ACID (7.18%), C22:0 (0.44%) & STERCULIC ACID (2.96%). MALVALIC & STERCULIC ACIDS WERE DETERMINED AS SILVER NITRATE-METHANOL DERIVATIVES OF THEIR METHYL ESTERS.

EXCEPT FOR THE PRESENCE OF 9% MALVALIC ACID & 6% STERCULIC ACID THE FATTY ACID COMPOSITION OF CHORISIA SPECIOSA SEED OIL, AS DETERMINED BY THIN-LAYER & GAS-LIQ CHROMATOGRAPHY, WAS SIMILAR TO THAT OF COMMON SEED OIL.