Glucosinolates continued... -L17

Question 1

Using animals what types of studies have been used to find agents to treat cancer?

Answer 1

induce cancer into the animals by chemical carcinogens
then they look at the effects of agents to either prevent/block/inhibit the process
glucosinolates for example seem to be particularly effective at reducing cancer development

Question 2

What is the GST ratio test/control?

Answer 2

its a way of measuring the potential protective effects an agent from diet on cancer
the higher the ratio the better the agent is at inducing phase 2 enzyme activity which promotes excretion of carcinogens

Question 3

What are some examples of compounds that have high GST ratio test/control ?

Answer 3

p-methoxyphenol, 2-BHA coumarin but particularly benzyl isothiocyanate

Question 4

What is the BP-induced tumours in rat fore stomach test/control value?

Answer 4

this is another ratio used to determine if a compound is beneficial for reducing cancer
if the ratio=1 then the compound has no effect
if the ratio 1 then the compound potentiates cancer

Question 5

What can the glucosinolate sinigrin do ?

Answer 5

it can suppress CYP1A1 transcription which is a phase 1 enzyme so this may be beneficial for reducing production of a carcinogen but its unknown yet
it can induce QR activity which is beneficial because it is a phase 2 enzyme

Question 6

What can glucoiberin do ?

Answer 6

it can suppress CYP1A1 transcription which is a phase 1 enzyme so this may be beneficial for reducing production of a carcinogen but its unknown yet
it can induce QR activity which is beneficial because it is a phase 2 enzyme - it can induces its activity even more than sinigrin

Question 7

What can glucobrassicin do ?

Answer 7

this glucosinolate can induce CYP1A1 activity which is likely to not be beneficial

Question 8

What can both progoitrin and glucosinalbin do ?

Answer 8

they can both suppress CYP1A1 transcription

Question 9

What is a key fact about glucosinolates?

Answer 9

its important to realise that different glucosinolates have different activities and therefore different effects, so some may be beneficial whilst others may not be also helpful

Question 10

What is confusing about phase 1 and phase 2 enzyme activity ?

Answer 10

it is clear that potentiating phase 2 activity is beneficial however it is difficult to know whether you want to induce phase 1 activity or reduce it

Question 11

What can sulforaphane do ?

Answer 11

it induces GSTs and leads to reduced aflatoxin-DNA adducts and increased urinary excretion of aflatoxin N7-guanine- a biomarker of aflatoxin-caused DNA damage

Question 12

What are food-related carcinogens?

Answer 12

heterocyclic amines - cooked meats and PHip

polycyclic aromatic hydrocarbons- smoked foods

Question 13

Why is BBQ food bad?

Answer 13

because fatty acids from the meat can be formed due to the high temperatures

• these can produce BP- the fats hit the hot coals and it gets partially oxidised to various aromatic molecules and these get cooked back into the meat through smoke
• the BP is the oxidised by our liver enzymes producing BP diol epoxide - parts of this can fit between base pairs and others can react with nucleophiles on DNA
• BP diol expoxide then forms BP diol epoxide adduct with DNA - accumulation of these in your DNA can lead to cancer

Question 14

What is PhiP ?

Answer 14

it is a carcinogen that can be formed by high cooking temps of meat and fish and could contribute to diet related cancers
it is one group of compounds known as HCAs

Question 15

What can be determined about HCAs from a cooked beef meal?

Answer 15

absorption of HCAs is essentially complete and that urinary excretion of unchanged amine is indicative of the extent to which they are metabolised, as long as you know what went in to start with

Question 16

What can increase PhiP activation ?

Answer 16

increased induction of enzymes (particularly CYP1A1) increases PhiP activation which can be measured by looking for urinary metabolites

Question 17

When looking at urine what types of metabolites do you want to find?

Answer 17

want to find glucuronides and sulfates as they haven’t reacted with DNA
the guanine adducts wouldn’t be as good as they will have reacted with DNA

Question 18

What was shown about urinary excretion in human volunteers consuming cruciferous vegetables and cooked beef meals ?

Answer 18

increased excretion of the metabolic products of HCAs

• glucosinolates have at least increased phase 2 enzymes causing increased excretion of the good metabolites
• carcinogen is being excreted at a much faster rate when cruciferous veg are consumed

cruciferous veg consumption led to increased levels of N-hydroxy-PhiP glucuronide which is a major detoxification metabolite of PhiP in human urine - this clearly shows that the consumption of this veg enhances overall clearance of the carcinogen by glucuronidation

Question 19

What has been suggested about PhiP activation ?

Answer 19

its activation is increased by induction of enzymes involved in the activation of HCAs

Question 20

Why has it been difficult to prove that the consumption of cruciferous veg is beneficial?

Answer 20

because evidence proving that glucosinolates are beneficial hasn’t actually been found even if there appeats to be strong protective correlations

e.g looked at individuals with bowel cancer due to consumption of red meat which is suppose to enhance risk. however there is no evident differences in certain genes for enzymes that influence the effects of ingested HCAs
MAYBE WE ARE NOT MEASURING THE CORRECT PARAMETERS

Question 21

What other beneficial properties do glucosinolates have?

Answer 21

isothiocyanates stimulate apoptosis of human tumour cells in vitro
allyl isothiocyanate suppresses aberrant crypt foci in colon of rats treated with the chemical carcinogen DMH - soon after DMH application, allyl isothiocyanate stimulates apoptosis
allyl isothiocyanate present in mustard, sprouts and cabbage may act as a selective anti-carcinogenci inducer of programmed cell death

Question 22

What other factors can isothiocyanates react with ?

Answer 22

react with proteins
they are quite chemically active and reactive in many different ways - act on histidine groups, hydroxyl groups etc
this could be another route to directly or indirectly prevent cancer

Question 23

What proteins have been associated with isothiocyanates?

Answer 23

a whole range of proteins have been associated with them

- those involved in cell division by some aspect enabling them to act by many different pathways of cell division

Question 24

When do glucosinolates act in the pathway of the development of cancer?

Answer 24

they may act at many different points and this is beneficial because different glucosinolates have different activities

Question 25

What glucosinolates have no taste but can induce QR?

Answer 25

4-methylsulphinylbutyl GSL

3-methylsuphinylpropanyl GSL

Question 26

what glucosinolate has a pungent bitter taste?

Answer 26

2-propenyl GSL

Question 27

what glucosinolate has a mustard aroma?

Answer 27

3-butenyl GSL

Question 28

What glucosinolate is goitrogenic?

Answer 28

2-hydroxy-3-butenyl GSL-

this has a negative effect

Question 29

As glucosinolates have varying effects of which some are better than others what can be done to improve their effect?

Answer 29

conventional plant breeding or genetic modifications
- may be possible to alter taste so people who think they re bitter dont have that any more
- may be possible to increase levels of beneficial compounds
enhancing both of these effects would be very beneficial

Question 30

What is slowing down the research into specific foods helping to prevent cancer?

Answer 30

it is the fact that cancer is not mentioned in association with food because cancer is classified as a bad word to express even when a compound could be beneficial against it

Question 31

What differences were observed between fresh and frozen broccoli ?

Answer 31

the frozen ones had very similar levels of inducer activity however it was the same as the lowest level for fresh and this is because the cell structure is altered causing the release of enzymes
the levels of inducer activity in the fresh ones varies greatly - very different levels of tyrosinase activity

Question 32

What was seen when they looked at 3 day old sprouts ?

Answer 32

the levels of activity are substantially higher compared to the older broccoli therefore insinuating it is much better to eat 3 day old sprouts

Question 33

Why do 3 day old sprouts have such high inducer activity ?

Answer 33

contain 10-100 times more glucoraphanin- this is the precursor of sulfurophane which is a very potent phase 2 inducer
sprouts are more effective in inhibiting phase 1 enzymes than older plants

Question 34

What was originally thought about glucosinolates and what has now been established?

Answer 34

originally thought to be toxic so they tried to reduce their levels but then they realised they induced beneficial effects
actually their concentration varies their levels of beneficial activity therefore there is an optimum concentration to reach- too low and you increase risk of cancer but too high and this may cause liver and kidney damage

Question 35

What can affect the levels of glucosinolates in food?

Answer 35

the processing of food- therefore its been researched to see if we can process food for optimal health properties

Question 36

What is the link between garlic and gastric cancer mortality ?

Answer 36

increased garlic consumption appears to reduce gastric cancer mortality
in one study there was a 50% decline in risk for gastric cancer when high levels of garlic are consumed

Question 37

What happens to the number of DNA adducts when garlic is placed in the microwave?

Answer 37

at 60seconds its number of DNA adducts is substantially higher than if it is in the microwave for 30 seconds