- Email: [email protected]
Copper-containing IUDs are not associated with an increase of malondialdehyde levels in cervical mucus
CONTRACEPTION
COPPER-CONTAINING
IUDs ARE NOT ASSOCIATED WITH AN INCREASE
OF MALONDIALDEHYDE Arthur
LEVELS IN CERVICAL MUCUS
W. Bull+, Kamran Moghiss?,
Kay Wachsman*, and Lawrence J. Marnett + Department
+s
of Chemistry, Wayne State University Detroit, Michigan 48201
6 To whom correspondence * Department
should be addressed.
of Obstetrics and Gynecology
Wayne State University
School of Medicine
Detroit, Michigan 48202
ABSTRACT
The malondialdehyde (MDA) content of cervical mucus from 23 healthy adult females was measured usin an ion-pairing HPLC method ca able of detecting 10 pmol MDA. Ten of t5 e women were wearing copper IL?Ds, four an IUD. were wearing plastic IUDs, and nine controls were not wearin Buteal, and Cervical mucus was sampled during the follicular, periovulatory, menstrual phases. The study was desi ned to determine if there is a relationship between MDA formation and ta e use of a copper IUD. A total of 79 samples were analyzed. On1 16 of the samples had sufficient MDA for reliable quantitation with the leve Y ranging from 0.1 nmol/g to 2.32 nmol/g. In 19 of the samples, trace levels (co.06 nmol/g) were detected but could not be reliably quantitated. In the remaining 44 samples, no MDA was detectable. There was no correlation between the presence of copperor non-copper-containig IUDs and the level of MDA. These results are contrary to a previously published report that used a less specific method for MDA analysis. Introduction Malondialdehyde (MDA) is a three-carbon dialdehyde biological systems during prostaglandin and thromboxane biosynt lYqduced esis and asina result of lipid Peroxidation (l-3). MDA is weak1 mutagenic and is reported to be carcinogenic although recent studies, usin 7 Highly purified material, have romoting, or camp ete carcmogenic activity (4-6). not detected initiating, MDA is extremely unsta le at acidic H and ra idly binds to protein and pb nucleic acids (7,8). The metabolism of KDAtoCg” 2 1s quite rapid even after high doses
are administered
(9).
Recently it was reported that MDA could be detected in cervical mucus of women wearing copper IUDs, but not in mucus from women wearing inert Submitted for publication November 11, 19% Accepted for publication January 16, 1987
JANUARY
1987 VOL. 35 NO. 1
49
CONTRACEPTION
IUDs (10). Copper IUDs are the most effective intrauterine devices and are in widespread use throughout the world. An implication of the previous study was that a large number of women, who wear copper IUDs, are at risk of the chronic toxicological effects of MDA. In the reviously reported work, a polarographic method was used to measure M 8 A (11). The method is not specific for MDA and no procedure was incorporated to separate MDA from potential interfering impurities. The importance of an association between copper IUDs and the production of a ossible carcinogen prompted us to develop a s ecific and sensitive method for K DA quantitation and to appl it to groups o P women wearing copper IUDs, plastic IUDs, or no IUD at al ly This communication presents the results of these studies. PATIENTS
AND METHODS
Patients: Cervical mucus and menstrual blood samples were obtained from a total of 23 healthy women. Nine women aged 22-36 (mean 30.3) served
e menses. Cervical mucus and menstrual blood were collected by a tuberculin syringe without needle and then transferred to carbonate centrifuge tubes. After collection, the samples were which was within 48 hr of collection. Samples were at 100,000 x g for 1 hr, then the aqueous supernatant pellet with a microliter syringe and the volume recorded. The volume of sample obtained ranged from 2 ~1 to 500 ~1 following centrifugation. In some instances, the aqueous content of the sam le was too small (< 2 ~1) for analysis. Whenever possible, duplicate aliquots o P 10 fl were analyzed by ion-pairing HPLC accordmg to a previously published procedure (13). The MDA content was,quantitated by electronic integration based on absorbance at 267 nm. For most samples, a third injection was made to which authentic MDA was added. This was done to confirm the identity of the peak uantitated as MDA or to verify the osition of elution if no MDA was Stetected. The analyst had no prior know Pedge of the IUD status of the women from whom the samples were obtained. Methods:
To assess the recovery of MDA, authentic l4 C-MDA was added to a sample of cervical mucus then aliquots were centrifu ed and analyzed at various times. After storage at room temperature for 2 B hr, 96 % of the added MDA was detectable by HPLC analysis. Although not necessary for recovery of MDA, refri eration of the cervical mucus samples was done to prevent the formation of a J ditional MDA between the time of collection and analysis. RESULTS A total of 92 cervical mucus samples were collected of which 79 had sufficient aqueous material for HPLC analysis. Other than the samples
SO
JANUARY
1987 VOL.
35 NO.
1
CONTRACEPTION
collected at the time of menstruation (blood contamination), the anal st was unaware of the origin of a particular sample. The 13 samples that coul cy not be analyzed were evenly distributed between the follicular, periovulatory, and luteal phases. The level of MDA in the cervical mucus of women wearing a Co per-7 IUD is shown in Table I. Less than half the samples contained detectable KIDA. The levels ranged from trace amounts (co.06 nmol/g) to 1.43 nmol/g. There was no relationship between the presence of MDA and the phase of the menstrual cycle during which the sample was collected. Table I : MDA Levels in Cervical Mucus of Women Wearing Copper-7 IUD Phase of Cycle Code #
Follicular
Periovulatory
02
T’
T
0.12
T
04
T
T
T
N.D.3
06
__
T
__
0.38
09
0.16
N.D.
N.D.
N.D.
10
T
N.D.
1.43
N.D.
13
N.D.
T
N.D.
N.D.
144
N.D.
N.D.
N.D.
N.D.
16
N.D.
N.D.
N.D.
0.1
18
N.D.
N.D.
N.D.
__
24
N.D.
N.D.
__
N.D.
4/9
4/10
3/8
3/9
MDA present/ no. of samples
Luteal
Menses
1 T = possible trace level, ~0.06 nmol/g sample 2 numbers represent nmol MDA/g sample 3 N.D.= none detected 4 Cu-T IUD
Similar results were found in the cervical mucus of women wearin plastic IUDs. In this group only 4 of 13 samples contained any detectable MD w and the highest level found was 0.32 nmol/g. There were relative1 few patients in this roup since so few women use plastic IUDs. The resu Yts are summarized in igable II.
JANUARY
1987 VOL. 35 NO. 1
51
CONTRACEPTION
Table II: MDA Levels in Cervical Mucus of Women Wearing Lippes Loop Phase of Cycle Code #
Follicular
Periovulatory
Luteal
Menses
12
0.32l
N.D.2
N.D.
T3
17
N.D.
-_
N.D.
0.21
22
N.D.
N.D.
N.D.
T
23
__
N.D.
__
N.D.
o/3
o/3
3/4
MDA present/ no. of samples
l/3
r numbers represent nmol MDA/g sample 2 N.D. = none detected 3 T= possible trace level, co.06 nmol/g sample The highest frequency of detectable MDA was found in the cervical mucus of women who were not wearing either type of IUD. These data are shown in Table III. As in the other group, the amounts of MDA ran ed from trace levels to 2.32 nmol/g, the highest level found in any of the samp Bes.
DISCUSSION Bond et al.reported
detection of MDA in cervical mucus of 8 of 19 women (10). No MDA was detected in 21 women The MDA was quantitated b IUDs. issolved in 2 M HCl (11). The range of MD A7 to be 100 - 90 nmol. The limit of detection of the olarographic assay appears to be a proximately 100 nmol/g. MDA is a wea K mutagen in bacterial and mamma Plan cells and was reported to be a tumor initiator on mouse skin (4,5,12). The carcinogenicity of MDA is now in doubt (6). Nevertheless, findings of MDA in cervical mucus of women wearing copper IUDs established an indirect link between their use and the production of a weak genotoxic agent.
52
JANUARY
1987 VOL. 3.5 NO. 1
CONTRACEPTION
Table III: MDA Levels in Cervical Mucus of Women not Wearing an IUD Phase of Cycle Code #
Follicular
Periovulatory
Luteal
Menses
03
T’
T
0.172
T
05
0.13
N.D.3
__
1.26
07
T
2.32
N.D.
N.D.
08
T
T
__
T
11
__
N.D.
N.D.
N.D.
15
0.95
N.D.
N.D.
0.45
19
0.48
N.D.
0.24
0.77 T
20
N.D.
N.D.
__
21
__
N.D.
__
N.D.
3/9
2/5
6/9
MDA present/ no. of samples
6/7
1 T = possible trace level ,
We reexamined this question using a direct and specific HPLC assay for MDA that is several orders of magnitude more sensitive than the polarographic assay described in the previous work (13). In the present study, ion-pairing HPLC was used to separate MDA from contaminatmg impurities and ultraviolet absorbance was used to quantitate material elutin from the column. The limit of detection was approximately 0.05 nmol/g. Ta e identity of MDA in the mucus samples was verified by recording its characteristic absorbance spectrum using a diode arra detector and by cochromatography with an authentic standard of MDA. K4DA was detected in a number of subjects but the levels (0.1 - 2.3 nmol/ 1 were much lower than previously reported. No systematic increase in M %A content was observed m sub’ects wearing copper IUDs compared to those wearin plastic IUDs or indivi d uals not wearing IUDs. In fact, the largest number oB sublects . with MDA and the highest concentrations were present in subjects not wearing IUDs.
JANUARY
1987 VOL. 35 NO. 1
53
CONTRACEPTION
The basis for the discrepancy between our results and those of Bond et alis not clear. The analytical methods are very different. The HPLC method is more specific and more sensitive than the olarographic method. Our protocol required minimal sam le handling and aR operations were carried out under conditions where MD 1. is maximally stable. The fact that the MDA levels in the present studv are nearlv 1000 times lower than those oreviouslv reoorted ques’tions the identity of the material quantitated as MDA b’ the polar0 ‘raphic orocedure. Aside from the obvious differences in analvtica Y methods, ti?e onlv ‘differences in the protocols appears to be that Bond et’ al.collected the mucus from women whose IUDs were being removed (10). In our investigations, mucus samples were removed from women still wearing their IUDs. Considering the low mutagenicity of MDA and its apparent lack of carcinogenicity, the trace amounts of it detected in cervical mucus appear to be of no toxicological significance. Variations in its levels in individuals appear to be random and not associated with the use of copper-containing or inert IUDs. ACKNOWLEDGEMENTS This work was supported by research rants from the National Cancer Institute (CA 22206) and G.D. Searle & Co. l! JM is a recipient of an American Cancer Society Faculty Research Award (FRA 243). REFERENCES 1.
Hamberg, M. and Samuelsson, B. Oxygenation of unsaturated fatty acids by the vesicular gland of sheep. J. Biol. Chem. 242: 5344-5354 (1967).
2.
Diczfalusy, U., Falardeau, I’., and Hammarstrom, prostaglandin endoperoxides to C T-hydrox acids thromboxane synthase. FEBS Lett. 84: $71-274 (IJ77).
3.
Schauenstein, E., Esterbauer, H., and Zollner., H. in Aldehydes in Biolo ical Systems, Their Natural Occurrence and Biological Activities (Gore, % .H. translator). Pion Ltd., London. 1977, pp 133-140.
4.
Basu, A.K. and Marnett, L.J. Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis (London) 4: 331-333 (1983).
5.
Shamberger, R.J., Andreone, T.L., and Willis, C.E. Antioxidants and cancer. IV: Initiatin activity of malonaldehyde as a carcinogen. J. Nat’l. Cancer Inst. 53: 1771-177 5 (1974).
6.
Fischer, S.M., Ogle, S., Marnett, L.J., Nesnow, S., and Slaga, T.J. The lack of on Sencar initiatin and/or promoting activit of sodium malondialdehyde mouse s8.m. Cancer Lett. 19: 61-66 r1983).
7.
Chio, KS. and Tappel, A.L. Inactivation of ribonuclease b peroxidizing lipids and by malonaldehyde. 2 i 27-2833 (1969).
8.
Brooks, B.R. and Klamerth, O.L. Interaction aldehydes. Eur. J. Biochem. 5: 178-182 (1968).
JANUARY
S. Conversion of by human platelet
and other enzymes Biochemistry 8:
of DNA with bifunctional
1987 VOL. 35 NO. 1
CONTRACEPTION
9.
Marnetf, L.J., Buck, J., Tuttle, M.A., Basu, AK, and Bull, A.W. and oxidation of malondialdehyde in mice. Prostaglandins (1985).
Distribution 30: 241-254
10.
Bond, A.M., Briggs, M.H., Deprez, P.R., Jones, R.D., and Wallace, G.G. Malonaldeh de m cervicalmucus associated with’ copper IUD. Lancet 1: 1087-1088 (1 B80).
11.
Bond, A.M., Deprez, P.R., Jones, R.D., Wallace, G.G., Polar0 ra hit method for the determination (malona Eide Kyde). Anal. Chem. 52: 2211-2213 (1980).
12.
Yau, T.M. Mutagenicity and c totoxicit of malonaldehyde cells. Mech. Aging Devel. 11: 137 -144 (19 7 9).
13.
Bull, A.W. and Marnett, L.J. Determination of malondialdehyde ion- airing high performance liquid chromatography. Anal. Biochem. 284- ‘190 (1985).
JANUARY
1987 VOL. 35 NO. 1
and Briggs, M.H. of propanedial in mammalian by 149:
55
COPPER-CONTAINING
IUDs ARE NOT ASSOCIATED WITH AN INCREASE
OF MALONDIALDEHYDE Arthur
LEVELS IN CERVICAL MUCUS
W. Bull+, Kamran Moghiss?,
Kay Wachsman*, and Lawrence J. Marnett + Department
+s
of Chemistry, Wayne State University Detroit, Michigan 48201
6 To whom correspondence * Department
should be addressed.
of Obstetrics and Gynecology
Wayne State University
School of Medicine
Detroit, Michigan 48202
ABSTRACT
The malondialdehyde (MDA) content of cervical mucus from 23 healthy adult females was measured usin an ion-pairing HPLC method ca able of detecting 10 pmol MDA. Ten of t5 e women were wearing copper IL?Ds, four an IUD. were wearing plastic IUDs, and nine controls were not wearin Buteal, and Cervical mucus was sampled during the follicular, periovulatory, menstrual phases. The study was desi ned to determine if there is a relationship between MDA formation and ta e use of a copper IUD. A total of 79 samples were analyzed. On1 16 of the samples had sufficient MDA for reliable quantitation with the leve Y ranging from 0.1 nmol/g to 2.32 nmol/g. In 19 of the samples, trace levels (co.06 nmol/g) were detected but could not be reliably quantitated. In the remaining 44 samples, no MDA was detectable. There was no correlation between the presence of copperor non-copper-containig IUDs and the level of MDA. These results are contrary to a previously published report that used a less specific method for MDA analysis. Introduction Malondialdehyde (MDA) is a three-carbon dialdehyde biological systems during prostaglandin and thromboxane biosynt lYqduced esis and asina result of lipid Peroxidation (l-3). MDA is weak1 mutagenic and is reported to be carcinogenic although recent studies, usin 7 Highly purified material, have romoting, or camp ete carcmogenic activity (4-6). not detected initiating, MDA is extremely unsta le at acidic H and ra idly binds to protein and pb nucleic acids (7,8). The metabolism of KDAtoCg” 2 1s quite rapid even after high doses
are administered
(9).
Recently it was reported that MDA could be detected in cervical mucus of women wearing copper IUDs, but not in mucus from women wearing inert Submitted for publication November 11, 19% Accepted for publication January 16, 1987
JANUARY
1987 VOL. 35 NO. 1
49
CONTRACEPTION
IUDs (10). Copper IUDs are the most effective intrauterine devices and are in widespread use throughout the world. An implication of the previous study was that a large number of women, who wear copper IUDs, are at risk of the chronic toxicological effects of MDA. In the reviously reported work, a polarographic method was used to measure M 8 A (11). The method is not specific for MDA and no procedure was incorporated to separate MDA from potential interfering impurities. The importance of an association between copper IUDs and the production of a ossible carcinogen prompted us to develop a s ecific and sensitive method for K DA quantitation and to appl it to groups o P women wearing copper IUDs, plastic IUDs, or no IUD at al ly This communication presents the results of these studies. PATIENTS
AND METHODS
Patients: Cervical mucus and menstrual blood samples were obtained from a total of 23 healthy women. Nine women aged 22-36 (mean 30.3) served
e menses. Cervical mucus and menstrual blood were collected by a tuberculin syringe without needle and then transferred to carbonate centrifuge tubes. After collection, the samples were which was within 48 hr of collection. Samples were at 100,000 x g for 1 hr, then the aqueous supernatant pellet with a microliter syringe and the volume recorded. The volume of sample obtained ranged from 2 ~1 to 500 ~1 following centrifugation. In some instances, the aqueous content of the sam le was too small (< 2 ~1) for analysis. Whenever possible, duplicate aliquots o P 10 fl were analyzed by ion-pairing HPLC accordmg to a previously published procedure (13). The MDA content was,quantitated by electronic integration based on absorbance at 267 nm. For most samples, a third injection was made to which authentic MDA was added. This was done to confirm the identity of the peak uantitated as MDA or to verify the osition of elution if no MDA was Stetected. The analyst had no prior know Pedge of the IUD status of the women from whom the samples were obtained. Methods:
To assess the recovery of MDA, authentic l4 C-MDA was added to a sample of cervical mucus then aliquots were centrifu ed and analyzed at various times. After storage at room temperature for 2 B hr, 96 % of the added MDA was detectable by HPLC analysis. Although not necessary for recovery of MDA, refri eration of the cervical mucus samples was done to prevent the formation of a J ditional MDA between the time of collection and analysis. RESULTS A total of 92 cervical mucus samples were collected of which 79 had sufficient aqueous material for HPLC analysis. Other than the samples
SO
JANUARY
1987 VOL.
35 NO.
1
CONTRACEPTION
collected at the time of menstruation (blood contamination), the anal st was unaware of the origin of a particular sample. The 13 samples that coul cy not be analyzed were evenly distributed between the follicular, periovulatory, and luteal phases. The level of MDA in the cervical mucus of women wearing a Co per-7 IUD is shown in Table I. Less than half the samples contained detectable KIDA. The levels ranged from trace amounts (co.06 nmol/g) to 1.43 nmol/g. There was no relationship between the presence of MDA and the phase of the menstrual cycle during which the sample was collected. Table I : MDA Levels in Cervical Mucus of Women Wearing Copper-7 IUD Phase of Cycle Code #
Follicular
Periovulatory
02
T’
T
0.12
T
04
T
T
T
N.D.3
06
__
T
__
0.38
09
0.16
N.D.
N.D.
N.D.
10
T
N.D.
1.43
N.D.
13
N.D.
T
N.D.
N.D.
144
N.D.
N.D.
N.D.
N.D.
16
N.D.
N.D.
N.D.
0.1
18
N.D.
N.D.
N.D.
__
24
N.D.
N.D.
__
N.D.
4/9
4/10
3/8
3/9
MDA present/ no. of samples
Luteal
Menses
1 T = possible trace level, ~0.06 nmol/g sample 2 numbers represent nmol MDA/g sample 3 N.D.= none detected 4 Cu-T IUD
Similar results were found in the cervical mucus of women wearin plastic IUDs. In this group only 4 of 13 samples contained any detectable MD w and the highest level found was 0.32 nmol/g. There were relative1 few patients in this roup since so few women use plastic IUDs. The resu Yts are summarized in igable II.
JANUARY
1987 VOL. 35 NO. 1
51
CONTRACEPTION
Table II: MDA Levels in Cervical Mucus of Women Wearing Lippes Loop Phase of Cycle Code #
Follicular
Periovulatory
Luteal
Menses
12
0.32l
N.D.2
N.D.
T3
17
N.D.
-_
N.D.
0.21
22
N.D.
N.D.
N.D.
T
23
__
N.D.
__
N.D.
o/3
o/3
3/4
MDA present/ no. of samples
l/3
r numbers represent nmol MDA/g sample 2 N.D. = none detected 3 T= possible trace level, co.06 nmol/g sample The highest frequency of detectable MDA was found in the cervical mucus of women who were not wearing either type of IUD. These data are shown in Table III. As in the other group, the amounts of MDA ran ed from trace levels to 2.32 nmol/g, the highest level found in any of the samp Bes.
DISCUSSION Bond et al.reported
detection of MDA in cervical mucus of 8 of 19 women (10). No MDA was detected in 21 women The MDA was quantitated b IUDs. issolved in 2 M HCl (11). The range of MD A7 to be 100 - 90 nmol. The limit of detection of the olarographic assay appears to be a proximately 100 nmol/g. MDA is a wea K mutagen in bacterial and mamma Plan cells and was reported to be a tumor initiator on mouse skin (4,5,12). The carcinogenicity of MDA is now in doubt (6). Nevertheless, findings of MDA in cervical mucus of women wearing copper IUDs established an indirect link between their use and the production of a weak genotoxic agent.
52
JANUARY
1987 VOL. 3.5 NO. 1
CONTRACEPTION
Table III: MDA Levels in Cervical Mucus of Women not Wearing an IUD Phase of Cycle Code #
Follicular
Periovulatory
Luteal
Menses
03
T’
T
0.172
T
05
0.13
N.D.3
__
1.26
07
T
2.32
N.D.
N.D.
08
T
T
__
T
11
__
N.D.
N.D.
N.D.
15
0.95
N.D.
N.D.
0.45
19
0.48
N.D.
0.24
0.77 T
20
N.D.
N.D.
__
21
__
N.D.
__
N.D.
3/9
2/5
6/9
MDA present/ no. of samples
6/7
1 T = possible trace level ,
We reexamined this question using a direct and specific HPLC assay for MDA that is several orders of magnitude more sensitive than the polarographic assay described in the previous work (13). In the present study, ion-pairing HPLC was used to separate MDA from contaminatmg impurities and ultraviolet absorbance was used to quantitate material elutin from the column. The limit of detection was approximately 0.05 nmol/g. Ta e identity of MDA in the mucus samples was verified by recording its characteristic absorbance spectrum using a diode arra detector and by cochromatography with an authentic standard of MDA. K4DA was detected in a number of subjects but the levels (0.1 - 2.3 nmol/ 1 were much lower than previously reported. No systematic increase in M %A content was observed m sub’ects wearing copper IUDs compared to those wearin plastic IUDs or indivi d uals not wearing IUDs. In fact, the largest number oB sublects . with MDA and the highest concentrations were present in subjects not wearing IUDs.
JANUARY
1987 VOL. 35 NO. 1
53
CONTRACEPTION
The basis for the discrepancy between our results and those of Bond et alis not clear. The analytical methods are very different. The HPLC method is more specific and more sensitive than the olarographic method. Our protocol required minimal sam le handling and aR operations were carried out under conditions where MD 1. is maximally stable. The fact that the MDA levels in the present studv are nearlv 1000 times lower than those oreviouslv reoorted ques’tions the identity of the material quantitated as MDA b’ the polar0 ‘raphic orocedure. Aside from the obvious differences in analvtica Y methods, ti?e onlv ‘differences in the protocols appears to be that Bond et’ al.collected the mucus from women whose IUDs were being removed (10). In our investigations, mucus samples were removed from women still wearing their IUDs. Considering the low mutagenicity of MDA and its apparent lack of carcinogenicity, the trace amounts of it detected in cervical mucus appear to be of no toxicological significance. Variations in its levels in individuals appear to be random and not associated with the use of copper-containing or inert IUDs. ACKNOWLEDGEMENTS This work was supported by research rants from the National Cancer Institute (CA 22206) and G.D. Searle & Co. l! JM is a recipient of an American Cancer Society Faculty Research Award (FRA 243). REFERENCES 1.
Hamberg, M. and Samuelsson, B. Oxygenation of unsaturated fatty acids by the vesicular gland of sheep. J. Biol. Chem. 242: 5344-5354 (1967).
2.
Diczfalusy, U., Falardeau, I’., and Hammarstrom, prostaglandin endoperoxides to C T-hydrox acids thromboxane synthase. FEBS Lett. 84: $71-274 (IJ77).
3.
Schauenstein, E., Esterbauer, H., and Zollner., H. in Aldehydes in Biolo ical Systems, Their Natural Occurrence and Biological Activities (Gore, % .H. translator). Pion Ltd., London. 1977, pp 133-140.
4.
Basu, A.K. and Marnett, L.J. Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis (London) 4: 331-333 (1983).
5.
Shamberger, R.J., Andreone, T.L., and Willis, C.E. Antioxidants and cancer. IV: Initiatin activity of malonaldehyde as a carcinogen. J. Nat’l. Cancer Inst. 53: 1771-177 5 (1974).
6.
Fischer, S.M., Ogle, S., Marnett, L.J., Nesnow, S., and Slaga, T.J. The lack of on Sencar initiatin and/or promoting activit of sodium malondialdehyde mouse s8.m. Cancer Lett. 19: 61-66 r1983).
7.
Chio, KS. and Tappel, A.L. Inactivation of ribonuclease b peroxidizing lipids and by malonaldehyde. 2 i 27-2833 (1969).
8.
Brooks, B.R. and Klamerth, O.L. Interaction aldehydes. Eur. J. Biochem. 5: 178-182 (1968).
JANUARY
S. Conversion of by human platelet
and other enzymes Biochemistry 8:
of DNA with bifunctional
1987 VOL. 35 NO. 1
CONTRACEPTION
9.
Marnetf, L.J., Buck, J., Tuttle, M.A., Basu, AK, and Bull, A.W. and oxidation of malondialdehyde in mice. Prostaglandins (1985).
Distribution 30: 241-254
10.
Bond, A.M., Briggs, M.H., Deprez, P.R., Jones, R.D., and Wallace, G.G. Malonaldeh de m cervicalmucus associated with’ copper IUD. Lancet 1: 1087-1088 (1 B80).
11.
Bond, A.M., Deprez, P.R., Jones, R.D., Wallace, G.G., Polar0 ra hit method for the determination (malona Eide Kyde). Anal. Chem. 52: 2211-2213 (1980).
12.
Yau, T.M. Mutagenicity and c totoxicit of malonaldehyde cells. Mech. Aging Devel. 11: 137 -144 (19 7 9).
13.
Bull, A.W. and Marnett, L.J. Determination of malondialdehyde ion- airing high performance liquid chromatography. Anal. Biochem. 284- ‘190 (1985).
JANUARY
1987 VOL. 35 NO. 1
and Briggs, M.H. of propanedial in mammalian by 149:
55