Preface

From the somewhat narrow perspective of the

industrialised Western world we often think of cancer
primarily as a disease of old age and affluence. In fact
the environmental influences upon cancer are extremely
complex. The geographical distribution of many cancers
spans cultures and age groups and there is compelling
statistical evidence to suggest that diet is amongst the
most important determinants of cancers such as carcinoma
of the oesophagus and stomach, which are common in the
Middle East and Asia. In the West, carcinoma of the
breast and colon are major causes of morbidity and death
which often begin in middle age and also seem strongly
linked to diet. Even lung cancer, for which the causal
connection with cigarette smoking is beyond dispute,
shows evidence of other environmental influences which
may include a protective effect of diet.
Epidemiological evidence makes it clear that diet can
protect against the development of cancer, and in some
circumstances promote it. Developments in molecular and
cell biology have recently led to significantly increased
understanding of cell proliferation and differentiation,
but there remains much to learn about the impact of diet
on these basic biological mechanisms. Food and Cancer
Prevention ' 9 2 was designed to explore these issues and
to promote, and facilitate, constructive
interdisciplinary interactions.
The meeting, held on the campus of the University of East
Anglia, represented the third in a series of biennial
conferences exploring the dietlhealth interface. The
first meeting (Bioavailability 8 8 ) , examined the area of
nutrient availability, whilst Fibre 90 focused on
dietary fibre. As befits a series of meetings organised
and underwritten by the Food Chemistry Group of the Royal
Society of Chemistry all three meetings emphasised the
central role of chemistry and chemists, and also served
to educate members of the profession in the challenges
and opportunities inherent in these exciting areas.

vi

Food and Cancer Prevention: Chemical and Biological Aspects

The concept of Food and Cancer 92 originated from a

workshop organised by RIKILT (State Institute for Quality
Control) and the Wageningen Agricultural University in
1990, and it is appropriate, therefore, that at the time
of writing a follow up meeting is being arranged for
1995. The field is rapidly moving and it is clear that
over the next few years there will be many advances in
techniques and understanding. It is to be hoped that the
ideas presented, and discussed, in Norwich will have
stimulated research, and encouraged progress.
The organisation of any meeting is a team effort. We are
very grateful to the Scientific and Organising Committees
for their hard work, to the numerous staff of the AFRC
Institute of Food Research for their unflagging
enthusiasm and efficiency, and to the Food Chemistry
Group for its financial support. In the end, of course,
the success of a meeting depends upon the participants
and we would finally like to thank all those who attended
the meeting.

K.W. Waldron
I.T. Johnson
G.R. Fenwick
January 1993

Contents

Part 1

The Relationships between Diet and

cancer in Human Populations

Food:

Its Role in the Etiology of Cancer

G.M. Williams, M.D.

Inhibition of Carcinogenesis by Non-nutrient

Constituents of the Diet

12

L.W. Wattenberg, M.D.

Contribution of Epidemiology in Elucidating the
Role of Foods in Cancer Prevention

24

D. Kromhout, H.B. Bueno de Mesquita and

M.G.L. Hertog
Work in Progress
T. Key, D. Forman, L. Cotton, A . Lewis,
G . Davey, J. Moore, G. Clark, C . Mlynek,
J. Tarrant, P. Savage, R . English and
B. Shepstone

Diet and Mammographic Patterns:

Workshop Report:

New Development in Epidemiology

37

42

W.P.T. James
Part 2

The Occurrence and Significance of

Carcinogens in Foods

Genotoxic Effects of Nitrosamines and Cooked Food

Mutagens in Various Organs of Mice and their
Modification by Dietary Factors
S. Knasmdller, W. Parzefall, W. Huber,

47

H. Kienzl and R . Schulte-Hermann

Influence of Sugar-linked- and Diallyldithiocarbamates on Mutagenic and Carcinogenic
N-nitroso Compounds

53

B.H. Lee, B. Bertram, P. Schmezer and

M. Wiepler
In Vitro Genetic Toxicology Testing of Naturally
Occurring Isothiocyanates
S.R.R. Musk and I.T. Johnson
Possible Clastogenic and Anticlastogenic Actions
of Fermented Milk I@Narinel@

A.K. Nersessian

58

62

...

Food and Cancer Prevention: Chemicaf and Biological Aspects

Vlll

Influence of Dietary Fat on Metabolism of 2-Amino3-Methyl-3H-Imidazo[4,5-f]Quinoline (IQ)

C . J . Rumney, I . R . Rowland and I . K . O'Neill

65

Influence of Diet on the Conversion of 2-Amino-3Methyl-3H-Imidazo[4,5-f]Qu~noline (IQ) t o the 7Keto Derivative (7-OHIQ)

70

C.J.

Rumney a n d I . R .

Rowland

Antimutagenic Action of Beta Carotene,

Canthaxanthin and Extracts of R o s m a r i n u s
O f f i c i n a l i s and M e l i s s a O f f i c i n a l i s Genotoxicity
of Basil and Tarragon Oil
A. B i a n c h i - S a n t a m a r i a , F. T a t e o and
L. S a n t a m a r i a
Nitrite-free Meat Curing Systems and the NNitrosamine Problem
F . S h a h i d i and R.B. Pegg

a2

Carbohydrates, especially Mono- and Disaccharides

in Excess Inhibit the Formation of Mutagenic
Heterocyclic Amines during Frying of Meat
K.I. Skog a n d I . M . J a g e r s t a d
Effects of Ellagic Acid, Tannic Acid and Quercetin
on the Mutagenic Activity of Cooked Food
Mutagens in the S a l m o n e l l a strain TA98
M. S t r u b e , P.A. Nielsen and J . C . L a r s e n
Analysis of Human Sera for Aflatoxin
A.P. W i l k i n s o n , D . W . D e n n i n g , H.A. Lee,
C.M. Ward a n d M.R.A. Morgan
Workshop Report: Dietary Carcinogenesis
Role in Human Cancer?

75

a7

92

97

What
102

W . Jongen

Part 3

Free Radical Reactions and Antioxidant

Nutrients in the Etiology of Human
cancers

Chemical Aspects and Biological Mechanisms of

Anticancer Nutrients in Plant Foods

109

D . I . Thurnham

Antioxidant and Pro-oxidant Actions of Dietary

Components
0.1. Aruoma and B . H a l l i w e l l

119

In V i t r o Antioxidant Activity of Lutein

M. Chopra a n d D . I . Thurnham

125

Effect of Vitamin A Dietary Intake on DNA Damage

Induced I n V i t r o by AFBl
S. Decoudu, P. C a s s a n d , V . C o l i n , B . Koch a n d

130

J.F.

Narbonne

ix

Contents

Availability of Soluble All-trans Versus 9-Cis

Carotene

8133

G. L e v i n and S . Mokady

Effects of Dietary Anticarcinogens on Rat Hepatic

and Intestinal Glutathione S-transferases
W.A. N i j h o f f and W.H.M.
Peters
Quantitation of Provitamin-A and Non-provitamin-A
Carotenoids in the Fruits most Commonly Consumed
in Spain
B . O l m e d i l l a , F . Granado, I . Blanco and

139

141

E . Rojas-Hidalgo

Seasonal Variation of Serum Levels of 8-Carotene

and a-Tocopherol
M. R a u t a l a h t i , D . A l b a n e s , J . Haukka, E . ROOS,
J. V i r t a m o

146

Antioxidant Vitamins or Lactulose as

Chemopreventive Agents for Colorectal Cancer
L. R o n c u c c i and M. Ponz d e L e o n

147

Carotenoids plus Vitamin A in Cancer Prevention,

Adjuvant Therapy, and Mastalgia Treatment
L. S a n t a m a r i a and A . B i a n c h i - S a n t a m a r i a

151

Workshop Report:
Protection
D.G.

Part I

Role of Anti-oxidants in Cancer

159

Lindsay

Tunour initiation: The Significance of

Endogenous Biotransformation Enaymes
and their Modulation by Diet

Modulation of Biotransformation Enzymes by NonNutritive Dietary Factors

P . J . van B l a d e r e n

163

Effect of Cooking and of Vegetables and Fruit on

1,2-Dimethylhydrazine-induced Colon
Carcinogenesis in Rats
G.M. A l i n k , H . A . Kuiper, V.M.H. H o l l a n d e r s and

175

J.H.

Koeman

Studies of Antimutagenic Factors in Food

G . B r o n z e t t i , E . Morichetti, C . S a l v a d o r i a n d
C . D e l l a Croce

iao

Does the Type of Fat Influence Intestinal and

Hepatic Microsomal Metabolism?
R. C h i n e r y , R . A . G o o d l a d , N . A . W r i g h t and

185

J.T.

Borlak

Food and Cancer Prevention: Chemical and Biological Aspects

Chemical and Biochemical Basis for Beneficial

Effects of Sulfhydryl Compounds on Food Safety

193

M . Friedman

Determination of Potentially Anticarcinogenic

Flavonoids in Foods and Preliminary Results on
Daily Intake in The Netherlands
M.G.L. H e r t o g , P.C.H. Hollman and D . Kromhout
The Content of the Potentially Anticarcinogenic
Ellagic Acid in Plant Foods
P.C.H. Hollman and D . P . Venema
Inhibitory Effect of an Extract of Leaves of
R o s m a r i n u s O f f i c i n a l i s L. on Tumor Initiation
and Promotion in the Skin of CD-1 Mice
M-T. Huang, C-T. Ho, Z.Y. Wang, K . S t a u b e r ,
C . G e o r g i a d i s , J.D.

L a s k i n and A.H.

203

20 9

Conney

Vitamin A as a Modulator of I n V i t r o Unscheduled

DNA Synthesis Induced by 2-Amino-3Methylimidazo[4,5-f]Quinoline and 2-Amino-3,4Dimethylimidazo[4,5-f]Quinoline in Rat
Hepatocyte Primary Cultures
B . Koch, S. B l o w e r s ,
J . F . Narbonne

198

214

I . Rowland a n d

Comparison of Hydroxylated and Non-Hydroxylated

Natural Flavonoids as In V i t r o Modulators of Rat
Hepatic Benzo(a)Pyrene Metabolism
A.M. L e Bon, L . Z i e g l e r and M. S u s c h e t e t

2 17

The Distribution of Quercetin and Quercetin

Glycosides in Vegetable Components of the Human
Diet
T . L e i g h t o n , C. Ginther and L. F l u s s

223

I n Vivo Studies on Antigenotoxic Effects of NAPhytate and L . C a s e i in the Gastrointestinal

Tract of Rats
B . L . Pool-Zobel, B . B e r t r a m , K . D . J a n y ,
U. S c h l e m m e r and W . H . H o l z a p f e l

233

Desmutagenic Effect of Vegetables on Mutagens and

Carcinogens and Growth-inhibiting Effect of
Spinach Components on Cultured Human Cancer
Cells
K . S h i n o h a r a , M . Kobori and Z-L. Kong

238

Potential Anti-mutagenicity and Anticarcinogenicity of Some Plant Phenols

R . W a l k e r , A.D.

243

A y r t o n and C. I o a n n i d e s

Inhibition of Nitrosamine-induced Tumorigenesis by

Diallyl Sulfide and Tea
C . S . Y a n g , J - Y . Hong and Z-Y. Wang

247

xi

Contents

Part

Suppressing TUmour Development: The

Role of Diet in the Modulation of Cell
Proliferation

Role of Dietary Factors in the Modulation of

Cancer Induction
M.B.

255

Roberfroid

Diet and Breast Cancer

H . L . B r a d l o w , N . T . T e l a n g , J.J. M i c h n o v i c z and

270

M.P. Osborne

Proliferative Activity in the Colon of Healthy

Subjects in Two Italian Cities with Different
Dietary Habits
G . C a d e r n i , F. B i a n c h i n i , M.T. S p a g n e s i

275

Effects of Short chain Fatty Acid Infusion on the

Gastrointestinal Epithelium of Intravenously Fed
Rats

280

R . A . Goodlad, R . C h i n e r y , C . Y . Le e ,
M . A . G h a t e i , S . R . B l o o m and N . A . W r i g h t
I n V i t r o Studies into the Selective Toxicity of

Ally1 Isothiocyanate towards Transformed Human

Tumour Cells

285

S . R . R . Musk and I . T . Johnson

Cancer Preventive Agents in Processed Garlic

290

H . Nishino

Omega 3 Fatty Acids Suppress Mucosal Crypt Cell

Production in Rats

295

J . D . P e l l , J . C . Brown and I . T . Johnson

Workshop Report: Increased Cell Proliferation as

a Cause of Human Cancer

300

R . Goodlad

Workshop Report:
Candidates

Dietary Protective Factors

- New

3 02

L . Wattenburg

Part 6

Immune Mechanism: The Role of Food

Components as Immunoregulators

Bioactive Cell Wall and Related Components from

Herbal Products and Edible Plant Organs as
Protective Factors
K.W.

307

W a l d r o n and R . R . S e l v e n d r a n

Anti-tumorigenic and Immunoactive Protein and

Peptide Factors in Foodstuffs (I)
Antitumorigenic Protein from Tricholoma Matsutake
Y . Kawamura and M . I s h i k a w a

327

Food and Cancer Prevention: Chemical and Biological Aspects

xii

Anti-tumorigenic and Immunoactive Protein and

Peptide Factors in Foodstuffs (11)
AntiTumorigenic Factors in Rice Bran

Y. Kawamura a n d M . Muramoto
Part 7

Dietary Fibre and Related substances

Plant Cell Wall Material and Cancer Protection

S.A.

331

339

Bingham

Lignans and Isoflavonoids of Dietary origin and

Hormone-dependent Cancer

H. A d l e r c r e u t z , M . C a r s o n , Y . Mousavi,

348

P a l o t i e , S . Booms, M . L o u k o v a a r a ,
T . Makela, K. Wahbla, G . Brunow and T . Hase

A.

Bile Acids in a Human Model of Colorectal

Neoplasia
D.M. B r a d b u r n , I . R . R o w l a n d , J . C . Mathers,
A . Gunn, J . B u r n and I.D.A. J o h n s t o n
Variations of Colonic Proliferation, Cecal and
Fecal pH in Rats fed Different Carbohydrates
G . C a d e r n i , C . L u c e r i and M.T.

353

358

Spagnesi

Insoluble Dietary Fibre Rich Fractions from Barley

Protect Rats from Intestinal Cancers
G.H. McIntosh, L . J o r g e n s e n and P . R o y l e

362

Dietary Fibre and the Gastrointestinal Epithelium:

Differential Response in the Stomach, Small
Intestine and Colon of Conventional and Germfree Rats
B . R a t c l i f f e , C . Y . L e e , N.A. W r i g h t and

364

R.A.

Goodlad

Influence of Dietary Fibers on Two Intestinal

Transferases in Rats Inoculated with a Whole
Human Faecal Flora
N. R o l a n d , L . Nugon-Baudon, 0 . S z y l i t
Nitrite-Binding Properties of Dietary Fibres

369

374

F . S h a h i d i and C . Hong

Workshop Report: Non-starch Polysaccharides (NSP)

and Colorectal Cancer: The Current Position

379

S . Bingham

Part 8

Research Technique:

New Approaches

Toxicological Methods to Study Mechanisms of

Naturally Occurring Anticarcinogens
W.M.F.

Jongen

383

xiii

Contents

Isolation and Identification of Putative

Carcinogens and Anticarcinogens from Dietary and
Faecal Samples by Supercritical Fluid Extraction
and HPLC
A.D'Odorico, I.T. Gilmore, A . Morris,
A.J. Young and R . F . Bilton
Cell Proliferation and Morphometry in Endoscopic
Biopsies
R . A . Goodlad, S . Levi, C.Y. Lee and
N . A . Wright

396

401

Detection of Abnormal Mucosal Cell Replication in

Humans: A Simple Technique
J . A . Matthew, J.D. Pell, A. Prior,
H.J. Kennedy, I.W. Fellows, J.M. Gee and
I.T. Johnson

406

Rapid Detection of Inducers of Enzymes that

Protect Against Carcinogens
H.J. Prochaska, A.B. Santamaria and P. Talalay

411

Isolation and Identification of the Principal

Inducer of Anticarcinogenic Protective Enzymes
from Broccoli
Y. Zhang, P. T a l a l a y , C.-G. C h o and G.H.
Posner
Quatitation of Isothiocyanates by
Cyclocondensation with 1,2-Benzenedithiol
Y. Zhang, C-G. Cho, G.H. Posner end P. Talalay
The Biological Assay of Natural Mutagens using the
P53 Gene
C.E. Couet, A . B . Hanley, S. Macdonald and
L. Mayes
Workshop Report:
Methodologies
0.I. Aruoma

Research Techniques

421

426

In Vivo

Workshop Report: In Vitro Methodology

G. Williamson
Part 9

416

429

435

Implications for Public Health

Implications for Dietary Guidance

W.P.T. James

439

Subject Index

453