Interrelationships of dietary protein level, aflatoxin B1 metabolism, and hepatic microsomal epoxide hydrase activity

Biochemical studies during aflatoxin B1‐induced liver damage in rats fed different levels of dietary protein

“…Preston et al (I 976) found that less aflatoxin became attached to DNA when incubated with liver of a rat fed a lowprotein diet. Adekunle et al (1977) showed that in vitro production of aflatoxin M, (AFMl), a metabolite of AFBl, is decreased by a 5 % protein diet, when compared to 20% protein. This is probably due to the decreased levels of cytochrome P-450 found in the livers of these same rats.…”

Nutritional Renaissance and Public Health Policy

“…Because animal protein promotion of liver cancer appeared to be so substantial, convincing and provocative, the responsible mechanism was sought. Higher dietary protein (20% of calories versus 5%) 1) increased MFO enzyme activity 3- to 4-fold [ 21 – 26 ], 2) increased MFO-catalyzed activation of aflatoxin [ 21 ] to 3) a highly reactive epoxide of aflatoxin that covalently bonds to DNA [ 27 ] and produce mutations [ 28 , 29 ], 4) increased the number and/or size of pre-neoplastic cells in a dose-dependent manner (although this increase started at the recommended level of 10% protein) [ 30 , 31 ], 5) diverted dietary energy (calories) away from its normal, healthy support of voluntary exercise [ 32 ] and basal metabolism 6) through increased thermogenesis and greater brown adipose tissue activity [ 33 , 34 ] thereby favoring greater growth of cancer [ 35 , 36 ], 7) increased IGF hormone production (observed in a companion liver cancer mouse model that was initiated by hepatitis B virus and promoted by protein) [ 37 ], 8) increased production of reactive oxygen species [ 38 ] known to promote cancer [ 39 ], 9) depressed natural killer cell activity that destroys cancer cells [ 40 ] and, ultimately, 10) increased mature tumor formation and early death [ 33 , 41 – 43 ]. Also, increased dietary protein compromised DNA repair activity (unpublished).…”

Nutrition and Cancer: An Historical Perspective.—The Past, Present, and Future of Nutrition and Cancer. Part 2. Misunderstanding and Ignoring Nutrition

“…First, epidemiological associations of nutritional experience with cancer are far more convincing than associations of carcinogen exposure with cancer (17) and, second, all initiating carcinogens are dependent on activation by the cytochrome p450 system which itself is profoundly influenced by nutrition (15), especially by dietary-animal-based protein (29)(30)(31)(32)(33)(34). These findings have broad implications and seriously question the utility of the chemical carcinogen animal bioassay program.…”

“…Elevated dietary protein increases(a) MFO enzyme activity by three-to fourfold (29-34); (b) MFOcatalyzed activation of aflatoxin (29) to covalently bind to DNA (35) to cause mutations (36,37); (c) the number and/or size of microscopic clusters (foci) of preneoplastic cells in a dose-dependent manner, although this range of dietary protein begins at about 10% of diet calories that exceeds the recommended allowance (38,39) and ultimately; (d) mature tumors that cause premature death (40)(41)(42). The protein effect size is substantial at each of these disease mechanism stages, appearing within 8 days but even as early as 24 h after administration (43).…”