The use of yeast inoculation in fermentation for port production; effect on total potential ethyl carbamate

A commercial wine yeast Saccharomyces cerevisiae UCD 522 (pre-cultured in the presence of certain mass-labelled amino acids) was inoculated into a port must which was then allowed to ferment under controlled conditions of temperature and agitation. The influence of potential ethyl carbamate (EC) precursor formed due to yeast pre-culture, upon total potential EC levels was studied at various stages of fermentation. Pre-culture accumulation did not give rise to detectable levels of EC precursor during port fermentation

Induced cell proliferation and the initiation of skin tumour formation in mice by ultraviolet light

A single short exposure of the skin of mice to ultraviolet light did not produce any tumours, but a significant number of tumours developed when the exposure was followed by repeated applications of croton oil. Ultraviolet radiation therefore behaves as an initiating agent, resembling this action of some other carcinogens for the skin of mice. Treatment of the skin of the mice with acetic acid, xylene or croton oil 20 hours before irradiation increased the number of tumours. It is considered that cells induced to proliferate are more susceptible to the carcinogenic effect of ultraviolet radiation than their normal counterparts

The reaction of urethane with mouse liver nucleic acids In Vivo

Urethane, or a metabolite, has been shown to bind covalently to mouse liver DNA and protein, but not to RNA. Chromatographic examination of the acid hydrolysate of bound DNA showed that there was one radioactive peak which was separate from the major bases and nucleotides

Effects of partial hepatectomy on carcinogenicity, metabolism, and binding to DNA of ethyl carbamate

Male and female mice were given injections of ethyl carbamate at intervals after one-third or two-thirds hepatectomy. The incidence of hepatocellular tumors was increased after partial hepatectomy and correlated with both the number of cells synthesizing DNA at injection and the number of cells in mitosis. Partial hepatectomy did not affect the yields of lung tumors, liver hemangiomas, or the number and character of skin tumors if ethyl carbamate was followed by a promoting treatment with croton oil. More hepatocellular tumors occurred in males, but no sex differences in the numbers of liver hemangiomas, lung adenomas, or skin tumors were observed. The binding of an ethyl carbamate metabolite to liver DNA was fourteen times greater in males but the level of binding to lung or epidermal DNA showed no sex differences. Partial hepatectomy increased the binding to liver DNA in both sexes but did not alter the amount bound to lung or epidermal DNA. The rate of metabolism of ethyl carbamate was slower after partial hepatectomy, but this did not create a significant increase in the effective dose

The interaction of carbon-14-labelled alkyl carbamates, labelled in the alkyl and carbonyl positions, with DNA in vivo

The binding of ethyl carbamate labelled with carbon-14 in the alkyl or carbonyl group, and of methyl, n-butyl and n-propyl carbamates labelled in the alkyl group, to the DNA of mouse liver, lung and kidney has been studied in male Crackenbush mice. Only ethyl carbamate bound to liver and kidney DNA to any significant extent. The binding of ethyl carbamate labelled with carbon-14 in the C1, C2 or the carbonyl position was examined and compared. The levels of binding of [1-14C]- and [2-14C]ethyl carbamate to liver DNA were not significantly different (328 ± 34 and 267 ± 24 dpm/mg DNA, respectively), but there was very little binding of the [carbonyl-14C]ethyl carbamate (26 ± 3 dpm/mg DNA). Furthermore, only 18% of the radioactivity was removed from the DNA labelled with the alkyl-labelled carbamates, whereas 65% of the radioactivity was removed from the DNA labelled with carbonyl-labelled ethyl carbamate on continuous ether extraction. It was concluded that the bound molecule does not contain the carbonyl carbon and is probably an ethyl group

The prolonged binding of ethyl carbamate-(14C) to DNA in regenerating and intact mouse liver

The binding of ethyl carbamate-(1-14C), or a metabolite, to mouse liver DNA persisted longer if it was given to partially-hepatectomised mice compared with intact mice. Chromatographic examination of acid hydrolysates of the liver DNA from the partially hepatectomized mice showed that the radioactivity associated with the DNA was not present as a result of incorporation into the bases during DNA biosynthesis. Ethyl carbamate produced a greater inhibition of DNA turnover in the liver when given to partially-hepatectomized mice compared with intact mice

The interaction of [3H]ethyl carbamate with nucleic acids of regenerating mouse liver

The binding of [3H]urethane to liver DNA and RNA has been examined in partially hepatectomised and intact male Crackenbush mice. A single dose of [3H]urethane (50 μCi) was given to non-hepatectomised mice (group A) and to 3 groups of partially hepatectomised mice at 18 (B), 28 (C) and 38 (D) hours postoperatively, respectively. The binding was examined over the subsequent 16 h. The maximum levels of binding to DNA declined in the order, group A > B > C > D, although the binding to DNA persisted longest in group B. The binding to RNA was greater in groups B, C and D than in group A. Neither the restoration of liver mass nor an alteration in the metabolism of urethane appeared to account for the different levels of binding. In normal and partially hepatectomised mice a single dose of urethane (20 mg) was followed by an inhibition of mitosis and of the incorporation of [3H]thymidine into liver DNA and of [3H]uridine into liver RNA

Repeated partial hepatectomy as a promoting stimulus for carcinogenic response of liver to nitrosamines in rats

Partial hepatectomy 24 h before a single i.p. dose of dimethylnitrosamine, diethylnitrosamine or ethylmethylnitrosamine increased the carcinogenic response in the liver of rats as determined by the number of tumours and the number of "focal proliferations" produced. Secondly, in rats given a single i.p. dose of diethylnitrosamine, 3 partial hepatectomies 5, 10 and 15 weeks after dosing the animals increased the carcinogenic response in the liver. The stimulus of repeated partial hepatectomy therefore appears to act as a "promoting agent" for liver carcinogenesis, that is if the single dose of diethylnitrosamine is regarded as an "initiating agent" in the terms of the two-stage hypothesis