Glucosinolates continued... -L17 Flashcards Preview

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Flashcards in Glucosinolates continued... -L17 Deck (37):
1

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

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

2

What is the GST ratio test/control?

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

3

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

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

4

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

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

5

What can the glucosinolate sinigrin do ?

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

6

What can glucoiberin do ?

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

7

What can glucobrassicin do ?

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

8

What can both progoitrin and glucosinalbin do ?

they can both suppress CYP1A1 transcription

9

What is a key fact about glucosinolates?

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

10

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

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

11

What can sulforaphane do ?

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

12

What are food-related carcinogens?

heterocyclic amines - cooked meats and PHip
polycyclic aromatic hydrocarbons- smoked foods

13

Why is BBQ food bad?

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

14

What is PhiP ?

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

15

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

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

16

What can increase PhiP activation ?

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

17

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

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

18

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

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

19

What has been suggested about PhiP activation ?

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

20

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

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

21

What other beneficial properties do glucosinolates have?

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

22

What other factors can isothiocyanates react with ?

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

23

What proteins have been associated with isothiocyanates?

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

24

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

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

25

What glucosinolates have no taste but can induce QR?

4-methylsulphinylbutyl GSL
3-methylsuphinylpropanyl GSL

26

what glucosinolate has a pungent bitter taste?

2-propenyl GSL

27

what glucosinolate has a mustard aroma?

3-butenyl GSL

28

What glucosinolate is goitrogenic?

2-hydroxy-3-butenyl GSL-
this has a negative effect

29

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

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

30

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

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

31

What differences were observed between fresh and frozen broccoli ?

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

32

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

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

33

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

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

34

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

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

35

What can affect the levels of glucosinolates in food?

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

36

What is the link between garlic and gastric cancer mortality ?

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

37

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

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