US regulations to curb alleged cancer causes are ineffectual and compromised by scientific, constitutional and ethical violations.

The 1958 Delaney amendment to the Federal Food Drug and Cosmetics Act prohibited food additives causing cancer in animals by appropriate tests. Regulators responded by adopting chronic lifetime cancer tests in rodents, soon challenged as inappropriate, for they led to very inconsistent results depending on the subjective choice of animals, test design and conduct, and interpretive assumptions. Presently, decades of discussions and trials have come to conclude it is impossible to translate chronic animal data into verifiable prospects of cancer hazards and risks in humans.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on protein kinase C and inositol phosphate metabolism in primary cultures of rat hepatocytes.

Adult rat hepatocytes, after maintenance for 24 h in serum-free culture, were treated with the tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Short-term treatment (15 min) with TPA, 1 microM, increased protein kinase C (PKC) activity in the particulate fraction of hepatocytes and, concomitantly, decreased the vasopressin (100 nM)-stimulated synthesis of inositol phosphates. The latter effect of TPA could be prevented by prior addition of the PKC inhibitor, H7 (100 microM).

Mutagenic and antimutagenic effects of 5-substituted 2'-deoxyuridines depending on the nature of the 5-substituent.

Various 5-substituted pyrimidine 2'-deoxyribosides with anti-herpes activity were investigated for their genotoxic activity. 5-Iodo-2'-deoxycytidine (IDC), 5-(2-chloroethyl)-2'-deoxycytidine (CEDC), 5-(3-chloropropyl)-2'-deoxyuridine (CPDU), (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 5-ethyl-2'-deoxyuridine (EDU), 2'-deoxyuridine (DU) and 2'-deoxythymidine (DT) were non-mutagenic in Salmonella typh. as well as in V79 Chinese hamster cells, 5-Iodo-2'-deoxyuridine (IDU) was moderately mutagenic and 5-(2-chloroethyl)-2'deoxyuridine (CEDU) was highly mutagenic in V79 cells; neither IDU nor CEDU were mutagenic in the bacterial assay.

A quantitative evaluation of promoter activity by microinjection of chloramphenicol acetyltransferase hybrid genes into tissue culture cells.

The combination of DNA microinjection into tissue culture cells and the chloramphenicol acetyltransferase enzyme assay has been used to determine quantitatively the transcriptional activity of viral or eukaryotic promoters. As shown for a wide range of DNA concentrations and time periods between 2 and 16 h the assay allows the reliable and reproducible determination of promoter activities in defined cellular backgrounds. Only 50 cells are necessary for the test.