Short-term pregnancy hormone treatment of N-methyl-N-nitrosourea-induced mammary carcinogenesis in relation to fatty acid composition of serum phospholipids in female Lewis rats.
OBJECTIVE
Short-term oestrogen and progesterone treatment (STEPT) mimics the pregnancy hormone milieu. This study compared the development of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Lewis rats that received STEPT in early or later life.


METHODS
Rats in Groups 1 and 2 received a single intraperitoneal injection of 50 mg/kg MNU at 4 weeks old. Pellets containing 0.5 mg 17beta-estradiol and 32.5 mg progesterone (EP) were subcutaneously implanted in rats in Group 1 during 6-9 weeks old. Rats in Groups 3 and 4 received 50 mg/kg MNU at 22 weeks old and again at 23 weeks old. EP pellets were implanted in rats in Group 3 during 24-27 weeks old. At the time of EP removal and 8 weeks afterward, 4 randomly selected rats in each group were sacrificed for blood sampling. The fatty acid composition of serum phospholipids was measured by capillary gas chromatography. The remaining rats were sacrificed when they developed mammary tumours >or=1 cm in diameter or at the termination of the experiment, which was at 18 weeks old for Groups 1 and 2 and at 64 weeks old for Groups 3 and 4. Mammary cancer was histologically confirmed.


RESULTS
Group 1 had a significantly suppressed incidence of mammary cancer compared to Group 2 (7% vs. 90%), whereas the cancer incidence in Group 3 was similar to that of Group 4 (50% vs. 56%). Rats in Group 1 had significantly smaller n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and higher levels of docosahexaenoic acid (DHA) than those in Group 2 at the time of EP removal but not 8 weeks after EP removal. Neither the PUFA ratios nor the DHA levels differed between Groups 3 and 4 at any time. These data suggest that the age at which STEPT is administered is important, since its mammary cancer-suppressing potential was lost in aged animals.


CONCLUSIONS
DHA and the n-6/n-3 PUFA ratio may play a crucial role in mammary cancer suppression by STEPT.
Lai
Yen-Chang
YC
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Hamazaki
Kei
K
Yoshizawa
Katsuhiko
K
Kawanaka
Ayako
A
Kuwata
Maki
M
Kanematsu
Sayaka
S
Hamazaki
Tomohito
T
Takada
Hideho
H
Tsubura
Airo
A
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology; D008770:Methylnitrosourea / Q000633:toxicity*; D010743:Phospholipids / Q000097:blood* / Q000494:pharmacology*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics
D002273:Carcinogens; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea