JPS59219222A - Antimutagenic agent - Google Patents

Abstract

PURPOSE:An antimutagenic agent, containing L-cystine or reduced form glutathione as an active constituent, and capable of inactivating the mutagenicity caused by reaction of vitamin C with table luxuries. CONSTITUTION:An antimutagenic agent containing a thiol derivative expressed by the formula RSH (R is formula I or II) as an active constituent. As for reaction of an daily food or drink with vitamin C, it is known that the vitamin C is dissolved with coffee to produce mutagenicity in a magnitude of about 6 times of that of the coffee. The antimutagenic action against the mutagenicity caused by the vitamin C in L-cystine and the reduced form glutathione which are the thiol derivatives is found out. One mole vitamin C is mixed with one mole L-cystine or reduced form glutathione respectively to prevent the occurrence of the above-mentioned mutagenicity without deteriorating the activity of the individual vitamin C. This is a new knowledge of administering a large amount of the vitamin C.

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to an anti-mutagenic agent containing L-cysteine or reduced glu-j-thionta as an active ingredient.

(B) Background Art The present invention relates to an antimutagenic agent for reducing or completely inactivating mutagenicity in luxury goods, which is increased by vitamin C (also known as L-ascorbic acid).

Vitamin C has long been known as a special medicine for scurvy, and other benefits include colds, influenza, viral pneumonia,
It is thought to be effective against viral or bacterial infections such as hepatitis polio, measles, mumps, chickenpox, and tuberculosis.

In addition, in recent years, vitamin C has been shown to suppress the growth of malignant tumors (
H.Kawsaki et al. Cancer
Letters.

Vol. 16, 57-63.1982), report on inhibiting nitrosation reaction (S, 50M1rvish et a
lo, 5science.

Vol. 177.65-68.1972), and is an important substance from the viewpoint of preventing carcinogenesis.

Proposed by Dr. L. Pauling and others (E. Cameron e.
tal,.

Cancer Research, Vol, 39.66
3-68 L1979) is increasing, and the number of people who are actually taking large amounts of vitamin C in tablet form on a daily basis is increasing.

However, vitamin C has a strong reducing property derived from the enediol group in the molecule, and while it has beneficial physiological activities, it may also cause harmful reactions depending on the type of substances coexisting with it. In fact, vitamin C is mutagenic in the presence of copper ions (H, F, 5tich et a
l,, Natures Vol, 260e722-7
24.1976) and causing chromosomal abnormalities in animal cells (HJ, 5tich et al-, FdCosm
et, Toxicol,, Vol, 18.1197-
501゜1980), Methylcholane dilene (carcinogen)
(S, Banj, c, C
ancer Letters, Vol 11.239-2
42.1981) or act as an oncogenic promoter (K.

Imaida et al+, Proc, Jap-Ca
ncer As5nciation.

4th Ann-Meeting, T)79. 1
982) etc. have been revealed.

As for the reaction between daily foods and drinks and vitamin C, it is known that when vitamin C is dissolved with coffee, mutagenicity about 6 times that of coffee will be generated (Y-8uwa et al, +Mu ,t,a-t
ion Re5-, Vol-102, 3R3-691
, 1982).

Furthermore, the present inventor has revealed that the mutagenicity of luxury goods that we consume on a daily basis, such as tea, tobacco, and Z-hon whisky, is several times higher.

Today, when large amounts of vitamin C are consumed, providing vitamin C without causing any harmful reactions to the human body is the best way to prevent cancer. It can be said that this should be taken into account.

(q Disclosure of the invention Vitamin C is originally ingested from nature as a vitamin C complex along with other vitamins, and the current intake of large amounts of vitamin C alone is an extremely exceptional form of intake in terms of animal evolution. It is.

The present inventors believe that the above-mentioned mutagenicity caused by vitamin Gvc cannot be considered to be nontoxic to human cells, and furthermore, we believe that vitamin C can be used in vegetables, fruits, and vegetables to prevent such harmful reactions. Assuming that there is some substance that inhibits the reaction when ingested from vitamin C, we have conducted intensive research and found that L-cysteine, which is a thiol, and reduced glutathione have anti-mutagenic effects caused by vitamin C. It was discovered that it has mutagenic effects. Thiol compounds are known to cause mutagenic deactivation of methylglyoxal and aflatoxin B0 (Y, Fujita et al, Proc EMS).
Japan,, 'I l th Ann, Meeti
nP,, T) 113.1982M, Fr1ednn
, an et al., Fa Ghem, Toxi, c+
, Vol. 20°887-892.1982) is a new finding that thiol compounds deactivate the mutagenicity caused by the reaction between vitamin C and luxury foods.

L-cysteine and reduced glutathione have been used as a vitamin C stabilizing agent and a detoxifying/liver-protecting agent, respectively, and their antimutagenic activity has not been predicted. Therefore, by mixing these thiol forms Z with vitamin G, the activity of vitamin C itself is reduced.
'The use of vitamin C to prevent mutagenicity caused by the reaction with luxury foods or copper ions is a completely new matter.

According to experiments conducted by the present inventors, vitamin C increases the mutagenicity of coffee by about 6 to 10 times, but when 1 mole of L-cysteine or reduced glutathione is mixed with 1 mole of vitamin C, the effect is increased. The mutagenic Z can be suppressed as much as possible. Similarly, if black tea, tobacco, and straight bourbon are mixed with vitamin C, the increased mutagenicity caused by vitamin C can be suppressed.

IDI Example I) i Method for measuring the effect of suppressing heterogenicity and mutagenicity (il Method: Frequency method (cedar wood, long legs; Chemical Mutagiens, Vol. 6, p. 41, 19
According to 81).

(if strain used: histidine-requiring Salmonella,
Typhimurium (Salmonella, ivp
hi-murium) TA 100 shares (hereinafter referred to as “S”
(abbreviated as “Ti2O3 strain”).

(iii) Preparation of sample a) In the case of coffee: Dissolve instant coffee (powder) in distilled water. On the other hand, predetermined amounts of vitamin C1, cysteine, and glutathione (reduced form) (collectively referred to as "A#" under J Eng J) were dissolved in distilled water, and each solution was mixed to make 100 μl. Additionally, solutions of thiamine and vitamin E were similarly prepared as reference substances.

For tobacco: The tobacco particle phase collected with an automatic smoker (Chuo Sani) is treated with dimethyl sulfoxide (hereinafter referred to as "DMSO").
On the other hand, dissolve vitamin C1 and six or more of vitamin C1 and group A in distilled water, and mix each solution to make 100 μl.

c) In the case of alcoholic beverages: Dry the alcoholic beverage under reduced pressure at 40°C or less using a rotary evaporator, and add DMSO to the dried product to dissolve it. On the other hand, various components of vitamin C and group A were dissolved in distilled water, and each solution was mixed to give a total of 100μ7! Make it.

2) For black tea: Extract black tea at a ratio of 2.57 mm to 100 ml of boiled water, freeze-dry, and add distilled water to the dried product to dissolve it to a predetermined eA degree. On the other hand, various components of vitamin C and A group were dissolved in distilled water, and each solution was dissolved in yt
p, and make a total of 100 μl.

(+vl Measurement of mutagenicity ゛ Previous (+ij1, (a) ~ (, =l 100 μ/lc5 [I DPI!) of each sample obtained from l/C
100mM sodium phosphate buffer (TIH7,4
) and 10oμ/! S.

Add TA100 strain culture solution. After shaking this mixture at 37°C for 20 minutes, it was added to dissolved 2.5M soft agar and spread on a minimum glucose agar plate. In addition, 50 micromoles/plate of histidine, which is necessary to cause the bacteria to divide quantitatively on the plate, is added to the main plate. After standing at 67°C for 48 hours, the number of colonies on the plate is counted as a revertant strain. Nao, S9 mix (a combination of 9000!i' supernatant of rat liver homogenate and reduced nicotinamide adenine dinucleoside (NADPH)-producing thread) was not added.

(Result (1) Inactivation of mutagenicity caused by mixing vitamin C and coffee.

Table 1 shows that the increase in mutagenicity due to the reaction between coffee and vitamin C is about 10 times that of coffee alone, and also shows the antimutagenic activity of various ingredients. ))reactor. In the active arc, the mutagenicity when adding various ingredients is expressed as a percentage, taking the mutagenicity when coffee and vitamin C are mixed as 100.

Table 1 1-He “35
(9) l ′ + vitamin C" 372 (100) 1 + 't + cysti: "" 120
(32) 1+1 + reduced glutathione +'' 11
5 (31) 1 + , ・ 4 + 1 + Chia-kun 329 (88) p l
-z + Bipan E"314 (84) Side dish 6η/plate 1 bone 6 micromol/plate ---12 micromol/flat Vitamin C, t, or group A components alone are not found to be mutagenic. do not have.

According to Table 1, cysteine and reduced glutathione are found to have antimutagenic activity. Furthermore, thiamine and vitamin E had almost no antimutagenicity. In addition, the effects of the various components of group A do not extend to the mutagenicity of coffee itself, and as will be shown later, they have no antimutagenicity against the mutagenicity of straight bourbon or tobacco.
It specifically acts on the mutagenicity caused by vitamin C. In addition, its effect is found in vitamin C as a luxury item.
After confirming the increase in mutagenicity, the inactivating effect of thiamine pyrophosphate etc. was observed. This is thought to be an effect on radicals (active oxygen) generated by the reaction.

Inactivation of mutagenicity produced by mixing (il vitamin C and bourbon whiskey (straight) 2-Pon).

As shown in Table 2, the addition of vitamin C increases the mutagenicity of bourbon whiskey by more than five times. For this reaction, L-cysteine and reduced glutathione showed a strong antimutagenic effect.

On the other hand, the activity of thiamine was weak, and this effect was not observed for vitamin E.

Table 2 1 + Vitamin C”
596(100)z + # +L-cysteine"107(18)' + l (archetype glutathione 129(22)I + ! +thiamine 504(85)'+' +
Vitamin E"660 (110) Tatami 0.5ml/plate 3 micromol/plate ★Axle 12 micromol/plate (iiiil Vitamin C and tobacco (cigaret,
te smoke condenr, ate: CS
Inactivation of mutagenicity caused by the 1111 combination of C).

After collecting the particulate phase of cigarette smoke in a glass filter, D
A sample dissolved in MSO was used (C8C
). The mutagenicity caused by the reaction between C8C and vitamin C is L.
- Cystine, which can be eliminated by reduced glutathione. On the other hand, no effect was observed with thiamine and vitamin E. (Table 6).

Table 3 Bone Tobacco 14 (1
6)! +Vitamin C”
87 (100) # + # + L-cysteine 12 (14) da + l Bioreduced daltathion 12 (1, i) l 〃
+ Thiamine 80 (92) 1”
-# + Vitamin E 90 (10
3) Appetizer 0.25 m9/plate axis 6 micromol/plate ← 12 micromol/plate (1ψ Mutagenic inactivated vitamin C produced by mixing vitamin C and black tea mutates black tea as well) showed an effect of increasing mutagenicity (Table 4).This mutagenicity was caused by L-cysteine,
Completely inactivated by reduced glutathione. On the other hand, thiamin and vitamin E have no effect.

Table 4 Black tea 2H15)r + vitamin C” 139 (1
00) # + # ten-sistine
0(0)l + I Decimal glutathione 0(0)l + I + Thiamine
120 (86) l + I + vitamin E 145 (104) appetizer 0.25
WLl/plate 11 6 micromol/plate 12 micromol/plate (reservation) Industrial Applicability The present invention has demonstrated that the mutagenicity of various foods and luxury goods has been increased by 6 to 10 times by vitamin Cvc. Because it has an antimutagenic effect that dramatically reduces cancer, it can be effectively used in the medical field to prevent carcinogenesis.

At the same time, the vitamin C stabilizer t1. Because it is a detoxifying and visceral sieving agent, it is considered a safe additive for food and
Applications in the field of luxury goods are expected to be extremely wide-ranging.

Patent applicant: Suntory Ltd. (4 other people) Manual continuation supplementary book 1.Display of the incident 1982 Patent Application No. 95287 No. 2, Title of Invention antimutagenic agent 6. Person who makes corrections Relationship to the case Patent applicant address Name (190) Suntory Ltd. 4. Agent 6. Contents of amendment The specification is amended as follows.

Page Line Before correction After correction 5
12 Ban1c Ban1 and above

Claims (1)

[Claims] formula [In the formula, R is ( -(J2-a-cooH or H2 ■ It is. ] Antimutagenic part 1゜ containing a thiol form of as an active ingredient