Day 036 - 13 Oct 94 - Page 35


     
     1        models.  In the past few years our laboratory has been
     2        studying the impact of several confounding factors that
     3        could modulate the enhancing effect of fact on neoplastic
     4        development of the mammary gland in female rats which are
     5        treated with a carcinogen.  It is our conclusion that fat
     6        promotes carcinogenesis only under a very stringent set of
     7        conditions which might  not be duplicated in the arena of
     8        fat intake and human breast cancer. Previous  studies on
     9        fat and mammary cancer in experimental models have used
    10        young virgin rats which are given a dose of carcinogen at
    11        a particular age.  The question arises as to whether the
    12        promoting effect of fat might be a consequence of the
    13        characteristics of the model.  We have supportive evidence
    14        showing that the following criteria must be satisfied in
    15        order for fat  enhancement of mammary carcinogens to be
    16        manifested: (a) carcinogen administered at a time when the
    17        mammary gland is exquisitely susceptible to tumour
    18        induction, (b) animals maintained on a semipurified diet,
    19        (c) ad libitum  feeding necessary, and (d) unusually high
    20        requirement of linoleic acid for tumour development.  On
    21        the other hand, the stimulatory effect of fat is
    22        attenuated or sometimes even negated by (a) feeding of a
    23        natural ingredient diet, (b) submaximal calorie intake and
    24        (c) previous history of pregnancy and lactation.  Given
    25        the spectrum of confounders that are inherent in
    26        epidemiological studies linking fat intake and breast
    27        cancer, including differences in lifestyle, reproductive
    28        history, eating habits, as well as the complexity of the
    29        total diet, our findings suggest there may be a need to
    30        reevaluate the validity of extrapolating animal data that
    31        are obtained under a highly defined set of conditions to
    32        the aetiological significance of dietary fat in human
    33        breast cancer."  Academic Press Inc. 1993.
    34
    35        Please then turn, Dr. Barnard, to page 730.  At the bottom
    36        of page one find this:  "Complexity of Diet Composition -
    37        Conventional studies investigating the stimulatory effect
    38        of fat on carcinogenesis have used a purified diet which
    39        normally contains casein as the protein source together
    40        with a complement of simple and complex sugars.  The
    41        addition of standard vitamin and mineral premixes
    42        completes the formulation  of a nutritionally balanced
    43        diet. Experiments from the early work of Silverstone ...
    44        clearly demonstrated that animals fed a crude diet were at
    45        a lower risk of developing tumours than were those ped a
    46        purified diet.  We have similarly found that rats fed a
    47        natural-ingredient diet (N1H-07 open formula diet) were
    48        consistently less sensitive to DMBA-induced mammary
    49        tumourgenesis compared with  those fed a purified diet
    50        (AIN-76 formulation) over a wide range of fat levels. 
    51        Even in the presence of a high-fat intake, rats on a 
    52        natural-ingredient diet developed only half as many 
    53        tumours as those on a purified diet.  The attenuation of
    54        the fat effect by the natural-ingredient diet was
    55        reproducibly observed regardless of the protein level in
    56        the diet or the method of feeding, i.e. ad libitum feeding
    57        versus meal feeding.  The NIH-07 open-formula diet
    58        consists primarily of soybean meal, alfalfa meal and
    59        ground corn and wheat.  A vast array of chemicals with
    60        anticancer activity have  been identified in food, with

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