Bilateral ovariectomy and dietary administration of the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) are both effective inhibitors of chemical carcinogenesis in the rat mammary gland. The present study was designed to determine whether an enhanced inhibitory effect is obtained with combined ovariectomy and 4-HPR administration, compared to either treatment alone. In separate experiments, 50-d...

N,N'-Bis(2-chloroethyl)-N-nitrosourea (BCNU) is a sub strate for a microsomal enzyme of mouse liver. The reaction requires NADPH, and the product is 1,3-bis(2-chloro ethyl)urea. This activity is also found in mouse lungs but not in several other tissues. With reaction conditions under which BCNU is not chemically degraded, the Km for BCNU with liver microsomes is 1.7 mM; nicotine is a competiti...

We found previously that mouse mammary epithelial cells cultured in the presence of the mammogenic hormones progesterone and prolactin and treated with the carcinogen N-methyl-N-nitrosourea produced a high frequency of hyperplastic alveolar nodules and carcinomas with squamous metaplasia upon transplantation to syngeneic mice. The majority of these mammary transformants had an activated c-Ki-ra...

Prophage induction in lysogenic Escherichia coli W1709 (iota) was determined for 29 N-nitroso compounds, 13 of their denitrosated derivatives, and 7 hydroxylamino and hydrazino analogues of nitrosamines. Minimal inducing concentrations of 0.1 to 2.0 mug/ml were demonstrated for eight nitrosamidines, and concentrations of 0.5 to 25.0 mug/ml were shown for six nitrosamides. Weak inducing activiti...

An improved procedure for chemically decontaminating residues of nitrosoureas and related N-nitroso compounds ("nitrosamides") commonly used in the cancer research laboratory is proposed. Treatment of accumulated wastes with aluminum:nickel alloy powder while progressively increasing the basicity of the medium consistently led to at least 99.98% destruction of each nitrosamide tested. Hazardous...

The present study with N-methyl-N-nitrosourea and rat brain DNA was performed in order to study the distribution of alkylated products and the difference in the removal of these products from DNase I-sensitive and -resistant regions of DNA. Nuclei were isolated from N-[3H]methyl-N-nitrosourea-treated rats and incubated in the presence of DNase I (5 microgram/ml). Digested DNA was further hydrol...

N-nitroso compounds (NOCs) may be implicated in human colon carcinogenesis, but the toxicological mechanisms involved have not been elucidated. Because it was previously demonstrated that nitrosamines and nitrosamides, representing two classes of NOC, induce distinct gene expression effects in colon cells that are particularly related to oxidative stress, we hypothesized that different radical ...