Alcohol ingestion enhances hepatocarcinogenesis induced by synthetic estrogen and progestin in the rat.
We examined the effect of alcohol ingestion on rat hepatocarcinogenesis induced by oral administration of synthetic female hormones, 0.075 mg of ethynylestradiol (EE) and 6.0 mg of norethindrone acetate (NA), everyday for 12 months to Wistar rats. Concomitant administration of 10% ethanol in drinking water resulted in the development of hepatocellular carcinoma (HCC) in 40.8% in female rats and 11.8% in male rats at 12 months, although the incidences of HCC following hormones administration alone were 8.0% in female rats and 0% in male rats. The incidence and the number of hyperplastic nodules in rats with concomitant alcohol treatment were significantly higher than that in rats with hormone treatment alone. The additional alcohol administration significantly increased the values of nuclear and cytosol estrogen receptors at 4 months. Synthetic female hormones and/or alcohol treatment also significantly increased the value of cytosol progesterone receptor at 4 months. 32P-postlabeling analysis of liver DNA revealed that alcohol enhanced the DNA adduct formation induced by hormones. Consequently, alcohol may affect rat hepatocarcinogenesis caused by synthetic female hormones in enhancing cell-proliferating activity via estrogen and progesterone receptors, and DNA adduct formation induced by synthetic female hormones.
First Department of Surgery, Mie University School of Medicine, Japan.
K
K
Yamagiwa
R
R
Mizumoto
S
S
Higashi
H
H
Kato
T
T
Tomida
S
S
Uehara
K
K
Tanigawa
M
M
Tanaka
N
N
Ishida
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry; D004249:DNA Damage; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005260:Female; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000633:toxicity; D000077563:Norethindrone Acetate; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012737:Sex Factors
D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004997:Ethinyl Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone