Fr. Fullerton et al., ETHYNYLESTRADIOL PROTECTION AGAINST METHYL INSUFFICIENCY IN CASTRATEDMALE WISTAR FURTH RATS FED A METHIONINE-CHOLINE-DEFICIENT DIET, Carcinogenesis, 14(6), 1993, pp. 1237-1240
The interactive effects of dietary methyl insufficiency and the estrog
enic compound ethynylestradiol (EE) on the levels of S-adenosylmethion
ine (SAM) and S-adenosylhomocysteine (SAH) were examined in the liver,
lungs and pancreas of rats. In addition, such effects on the hepatic
content of 5-methyldeoxycytidine (5-MC) in nuclear DNA were determined
. Castrated male Wistar/Furth rats were fed various levels of EE in ei
ther: (i) a complete, amino acid-defined diet (diet 1); (ii) the same
diet lacking in choline and methionine and supplemented with 0.9% of D
L-homocystine (equimolar to methionine) (diet 2); or (iii) diet 2 but
only with 0.3% DL-homocystine (diet 2M). Methyl deficiency and EE each
independently produced decreased weight gains and increased relative
liver weights (liver weight relative to total body weight) compared wi
th control animals. Livers from rats fed diets 2 and 2M without EE had
lower levels of SAM and lower SAM:SAH ratios than did the livers from
diet 1-fed rats not treated with EE. Hepatic SAM:SAH ratios in diet 1
-fed rats were not altered by EE treatment. However, EE treatment incr
eased the hepatic contents of SAM and restored the SAM:SAH levels to n
ormal in rats fed diet 2 or 2M. The levels of SAM + SAH in the livers
of rats fed the low homocystine diet (diet 2M) were less than in those
fed either diet 1 or diet 2. Thus, the addition of EE at 10 p.p.m. ga
ve protection against reduced levels of SAM, and reduced SAM:SAH ratio
s in the liver, but had little effect when added to the methyl-adequat
e diet. No differences in hepatic 5-MC levels were observed in any of
the groups as a result of either methyl deficiency or EE treatment. Me
thyl deprivation alone caused no discernible difference in pancreatic
SAM levels but did result in a significant rise in SAH levels and thus
in decreased SAM:SAH ratios. EE had no consistent effect on pancreati
c SAM, SAH or SAM:SAH ratios in any of the diet groups examined. Simil
arly, the chronic feeding of diet 2, diet 2M or of EE had no significa
nt effect on the SA.M contents of lungs, compared with the correspondi
ng levels in control rats. The protection conferred by EE against SAM
insufficiency in the livers of rats fed a methionine- and choline-defi
cient diet is consistent with the relative insensitivity of female rat
s to the hepatotoxicity of dietary methyl insufficiency.