Tritiated thymidine as a broad spectrum initiator in transplacental two‐stage carcinogenesis, with phorbol as promoter

Abstract

A single subcutaneous injection of 200 mu Ci [3H] thymidine into pregnant BALD/c mice, followed by intraperitoneal injections of phorbol, twice weekly for 25 weeks, in the offspring, resulted in higher tumour development in the lungs and livers of male and, to a lesser extent, of female offspring, than in their untreated littermates. The difference in overall tumour incidence was statistically significant, but the increases of the individual tumour types were only of borderline significance. Slight carcinogenic activity of [3H]thymidine alone was observed in the mothers, and in the offspring, without phorbol treatment. The results suggest the possibility of using [3H]thymidine as a broad spectrum initiator for transplacental two-stage carcinogenicity studies to determine the organ specificity of different promoting agents.

Dietary Carcinogens and Anticarcinogens

“…However, one cup of coffee also contains about 250 mg of the natural mutagen chlorogenic acid (9) [which is also an antinitrosating agent (66)], highly toxic atractylosides (10), the glutathione transferase inducers kahweal palmitate and cafestol palmitate (11), and about 100 mg of caffeine [which inhibits a DNA-repair system and can increase tumor yield (99) and cause birth defects at high levels in several experimental species (100)]. There is preliminary, but not conclusive, epidemiologic evidence that heavy coffee drinking is associated with cancer of the ovary, bladder, pancreas, and large bowel (101).…”

Tension Transients in Single Isolated Smooth Muscle Cells

“…Physiologically, the relation between the level of gonadotropins secreted by the pituitary and DMBA hydroxylase activity indicates that the rate of ovarian cancer initiation increases under conditions of increased secretion of gonadotropins. This is supported by the finding that excessive stimulation of grafted rat ovaries by gonadotropins, in the presence or the absence of added xenobiotics, leads to an increase in ovarian cancer (21,22). Thus the action of gonadotropins on DMBA hydroxylase may be one of several hormone-dependent effects, including those at the level of gene expression and DNA replication.…”

Some basic problems in assessing carcinogenic risks

“…I might refer, in this connection, to our own current attempts at transplacental 2-stage carcinogenesis in animals, with a "broad-spectrum" initiator administered to the pregnant mother and the potential promoter to the offspring after birth (Armuth & Berenblum, 1979).…”