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Biomedical subjects

I Berenblum

Publications and source records attributed to I Berenblum.

At least 19 recordsLinked to original sources

Quantitative carcinogenesis in relation to human exposures.

While carcinogenic potency cannot be expressed in absolute terms, quantitative carcinogenesis nevertheless plays an important role both in assessing cancer risks and in devising effective methods of cancer prevention. Attention is drawn to newer methods of prevention based on interference with the carcinogenic process, which is likely to counterbalance, or even to reverse, the anticipated trend of increased cancer incidence resulting from new carcinogens introduced in our environment.

Carcinogens

The effect of caffeine on two-stage skin carcinogenesis and on complete systemic carcinogenesis.

A single large dose of caffeine (100 microgram/g body weight) was injected at different time in relation to urethan initiation for skin tumorigenesis, topical anthranil treatment serving as promotor. Caffeine significantly increased papilloma incidence when given 6 h before initiation, and to an insignificant extent, at 9 h prior to initiation. A tendency for inhibition was evident when caffeine was administered 6 h after urethan but this was also not statistically significant. Lung adenoma induction by urethan was unaffected. The significance of the timing of caffeine treatment in modifying the outcome of the initiation phase is discussed.

Adenoma

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

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.

Adenoma

Systemic promoting action and leukemogenesis in SWR mice by phorbol and structurally related polyfunctional diterpenes.

Phorbol and six structurally related compounds representing the polyfunctional diterpenes of the tigliane, ingenane, and lathyrane types were tested for systemic promoting and leukemogenic activity in SWR mice. For systemic initiation soon after birth, 15 microgram dimethylnitrosamine (DMN) was injected s.c. The diterpenes were administered i.p. either with or without prior systemic initiation with DMN. Systemic promotion was expressed for liver by induction of adenomas with all the diterpenes tested, some of them being more potent than phorbol. The relatively high dose of DMN used as initiator prevented an evaluation of promoting action in relation to lung carcinogenesis. The leukemogenic effect of phorbol in SWR mice was confirmed at three different dose levels. The other diterpenes tested had no significant leukemogenic activity. The leukemogenic action of phorbol was totally inhibited by prior DMN injection. The lack of correlation between promoting action in skin, systemic promoting action in liver and leukemogenic action, among the diterpenes tested, is discussed.

Animals

Mechanism of ovarian carcinogenesis: effect of 7,12-dimethylbenz[a]anthracene administration on intrasplenic ovarian grafts in unilaterally ovariectomized C3HeB/Fe mice.

A single oral administration of 7,12-dimethylbenz[a]anthracene (DMBA) 2 weeks after intrasplenic grafting of ovarian tissue in unilaterally ovariectomized C3HeB/Fe mice resulted in a high tumor incidence (47%) in the grafted tissue, with only 1 tumor (3%) in the orthotopic ovary. No tumors were seen in the control group (unilaterally ovariectomized mice given intrasplenic grafts of ovarian tissue without subsequent DMBA administration), nor did tumors develop in response to DMBA treatment in mice with both ovaries in situ and no grafted tissue in the spleen. The results indicated that some local change caused by the grafting procedure rendered the tissues more sensitive to the action of DMBA and/or more responsive to gonadotropic stimulation.

9,10-Dimethyl-1,2-benzanthracene

Carcinogenicity testing for control of environmental tumor development in man.

After briefly reviewing the present status of carcinogenicity testing as an aid to the control of environmental carcinogenesis in man, and discussing in somewhat more detail the relative advantages and limitations of animal testing and the two most widely used short-term assays--the Ames test and in vitro carcinogenesis--special attention is given to two points: 1) the difficulties inherent in extrapolating from the results of experimental tests an index of potential carcinogenic hazards in man; 2) the urgent need for additional testing procedures for the detection of associated factors (such as, cocarcinogenic factors and promoting agents) operating in human carcinogenesis.

Animals

Possible two-stage transplacental liver carcinogenesis in C57BL/6 mice.

A single SC injection of 2-acetylaminofluorene (AAF) was given to pregnant C57BL/6 mice on day 15 of gestation, and the offspring subsequently given twice-weekly injections of phorbol for 25 weeks. Control groups included: (1) untreated; (2) AAF-treated mothers (kept under observation for 18 months, as with all the other groups); (3) untreated offspring of untreated mothers; (4) untreated offspring of AAF-treated mothers, and (5) phorbol-treated offspring of untreated mothers. The incidence of hepatomas in the phorbol-treated offspring of AAF-injected mothers was 8/74 (11%), as compared with 2/80 (2.5%) in the untreated offspring of AAF-injected mothers. The AAF-injected mothers themselves developed 3/36 (8%) hepatomas; while all othe other control groups were free from liver tumours. The development of reticulum cell sarcomas, and of a few cases of lung adenomas, in the various groups, was presumably spontaneous. The results seem sufficiently encouraging, as a model for the study of systemic carcinogenesis, to warrant further attempts at two-stage transplacental carcinogenesis, using other potential initiators and promoters.

2-Acetylaminofluorene

Effect of colchicine injection prior to the initiating phase of two-stage skin carcinogenesis in mice.

Colchicine injected 5, 9 and 24 h respectively before initiation (using s.c. injection of urethane for initiating action and TPA skin applications for promoting action, in female ICR mice) led to a significant increase in skin tumour incidence in the --9-h group, and an increase in percentage malignancy in both the --5- and --9-h groups. These times corresponded to the peak of metaphase arrest by the colchicine. The results are discussed in relation in those of Pound and Withers (1963) and others, who found that mitotic stimulation at the time of urethane initiating action raised the ultimate tumour incidence; and the inference is drawn that initiating action in mouse skin may occur during the M phase, rather than during the G1, S, or G2 phases, as suggested by others.

Animals

Phorbol as a possible systemic promoting agent for skin carcinogenesis.

UNLABELLED: In a repetition of a previous experiment, using this time a 20-fold higher dose of phorbol, administered i.p. as potential (systemic) promotor for skin carcinogenesis, 6/22 (27%) of the treated mice (after a single skin application of DMBA as initiator) developed papillomas, as compared to 1/20 (5%) in the DMBA control group. Though the difference is statistically no more than of borderline significance (P less than 0.05), it does raise the possibility that unesterified phorbol is, after all, a weak promotor for skin carcinogenesis. ABBREVIATIONS: DMBA equals 7,12-dimethylbenz(a)anthracene. TPA equals 12-0-tetradecanoyl-phorbol-13-acetate.

9,10-Dimethyl-1,2-benzanthracene