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Biomedical subjects

L Tomatis

Publications and source records attributed to L Tomatis.

At least 73 records · Page 4Linked to original sources
PubMed1989

Increased tumour incidence and skin tumour promotion in two generations of descendants of 7,12-dimethylbenz[a]anthracene-treated pregnant mice.

Many experiments suggest the possibility of hereditary transmission of a predisposition to developing cancer. If this is the case, the progeny of animals exposed to carcinogens during embryogenesis should bear initiated cells. In order to examine this possibility, offspring of mice exposed to 7,12-dimethyl-benz[a]anthracene in utero were treated cutaneously with a tumour promoter, 12-O-tetradecanoylphorbol-13-acetate. This treatment resulted in the development of skin tumours, i.e., papillomas and carcinomas. Moreover, various tumours also developed in many internal organs, and particularly in the lung. These findings suggest that exposure to carcinogens may not only increase cancer risk in subsequent generations, but also considerably reinforce sensitivity to tumour-promoting factors, which by themselves may pose no threat to an unexposed population.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Overview of perinatal and multigeneration carcinogenesis.

One of the characteristics of recent decades, which have seen a formidable expansion of cancer research, has been the co-existence of the generally agreed hypothesis that most cancers are multifactorial in origin, with the attitude of concentrating nevertheless on single carcinogenic agents and on attempting to quantify cancer risks as if they were due to single factors. It is not possible at present to quantitatively estimate the role of prenatal exposures to carcinogens/mutagens in determining or modulating the risk of cancer in humans. It is not unreasonable to assume, however, that the consequences of prenatal exposures and of prenatal events are among the factors that are often ignored. Prenatal events can contribute to the occurrence of cancer as the consequence of either: (1) the direct exposure of embryonal or fetal cells to a carcinogenic agent; (2) a prezygotic exposure of the germ cells of one or both parents to a carcinogen/mutagen before mating; (3) a genetic instability and/or a genetic rearrangement resulting from selective breeding which may favour a deregulation of cellular growth and differentiation. By offering the possibility of investigating the role played by events involving both germ and somatic cells, studies on prenatal carcinogenesis may become essential for a more accurate estimation of risks attributable to environmental agents, and may at the same time contribute to the understanding of some of the mechanisms underlying the genetic predisposition to cancer.

Animals↗
PubMed1989

Role of oncogene activation during prenatal (transplacental) initiation and postnatal promotion of mouse skin tumours.

The transplacental initiation-postnatal promotion model of mouse skin carcinogenesis is useful in studying the molecular and cellular mechanisms of perinatal carcinogenesis. Offspring transplacentally exposed to an initiating dose of a carcinogen typically do not produce any skin tumours in the absence of postnatal treatment; many skin tumours appear only when they are treated with tumour-promoting agents postnatally. Tumour-promoting agents alone produce no skin tumours or only a few. Thus, two stages of carcinogenesis, initiation and promotion, can be conveniently separated. Our results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen. However, since postnatal promotion was essential for the production of tumours, they also suggest that a cell harbouring such a mutation may remain dormant until it encounters a tumour-promoting stimulus. Since a higher fraction of carcinomas than papillomas contained the specific mutation in Ha-ras, it is postulated that those papillomas with the point mutation have a selective advantage to progress towards carcinomas.

Animals↗
PubMed1988

The contribution of the IARC monographs program to the identification of cancer risk factors.

The differences between cancers that occur as a consequence of occupational exposure and other cancers are not only their preventability but, more importantly, their social unacceptability. Occupational cancer occurs, by definition, among individuals who have been exposed to carcinogens because of their occupation, and most, if not all, of these individuals are drawn from the less favoured social classes. This is probably one reason why mortality from cancer and from all causes is greater in people in classes IV and V than in those in I and II. We cannot precisely quantify the proportion of cases, among the total number of cancer cases observed, attributable to occupational exposures. It is very likely, however, in some of the most industrialized countries, although not in certain developing countries, that the number of those cancers that are indisputably due to occupational exposure is not increasing and is perhaps decreasing. This is due to the combined effect of two factors: the banning of certain chemicals, as, for instance, aromatic amines--even if this did not take place in all countries and, where it did, not at the same time; and improved working conditions, as, for instance, in the case of vinyl chloride. We do not know, however, to what extent low levels of exposure to which the general population is commonly exposed, as well as workers in occupations where levels of exposure to carcinogens have recently been significantly reduced, play a role in the causation of human cancer. While it is important to stress that a large proportion of the chemicals to which humans are exposed, either because of their occupation or in the general environment, and for which experimental evidence of carcinogenicity is available, have not been the object of epidemiological surveys, it is also important to realize that epidemiological methods are generally insufficient to provide reliable information on risks generated by low levels of exposure. It is certainly important to encourage epidemiological surveillance, but it should at the same time be made clear that the epidemiological approach will never entirely replace the considered use of experimental data in the implementation of primary prevention.

Humans↗
PubMed1988

Environmental cancer risk factors. A review.

The risk of cancer in humans is increased by a wide spectrum of factors, which ranges from exposure to an identified agent, such as environmental chemicals or a virus, to a culturally determined behaviour, such as smoking, or to socio-economic conditions. We are today able to intervene on some of these factors, while others affect risk by as yet undetermined pathways. Only progress in the understanding of the mechanisms by which these factors act can lead to specific means of cancer prevention. There is no compelling reason to believe that the number of carcinogenic agents, to which humans can be exposed, is infinite, nor is it unreasonable to assume that it will eventually be possible to identify most of them. The variety of cancer risk factors of which we are presently aware implies, however, that it would be impossible to have just one simple approach to cancer control and cancer prevention. It is rather encouraging that the applicability of new laboratory methods to epidemiological surveys seems to open the way to a laboratory-integrated epidemiology.

Diet↗
PubMed1988

[Transzygotic carcinogenic effect of nitrosoethylurea in rats].

The results of two experiments on the transzygotic transfer of the nitrosoethylurea (NEU) carcinogenic effect are presented. In the first experiment female rats received 60 mg/kg b. w. of NEU at 16, 18 and 20th day of the pregnancy. Their F1 descendants developed multiple tumours of the nervous system after a short latency (up to 40 weeks). The rats of F2, F3, F4 and F5 generations which were not in a direct contact with NEU developed a statistically higher incidence of tumours occurring spontaneously (those of mammary gland, pituitary, and haematopoietic tissue). However, the incidence of nervous system tumours was at the level of controls. In the second experiment male rats received 80 mg/kg b. w. of NEU and then were mated with untreated females. The incidence of the nervous system tumours in the descendants of treated males was somewhat higher than in the controls. The manifestations and mechanisms of the transzygotic effect are discussed.

Animals↗
PubMed1987

Transplacental induction of a specific mutation in fetal Ha-ras and its critical role in post-natal carcinogenesis.

Mouse skin tumors were produced after transplacental initiation [with 7,12-dimethylbenz(a)anthracene], only when the skin was treated post-natally with a tumor-promoting agent (12-O-tetradecanoyl phorbol 13-acetate). DNA analysis of tumors showed that all carcinomas analyzed contained a specific mutation (A to T transversion) at the 61st codon of c-Ha-ras. Fifty per cent of the papillomas analyzed also had this same mutation. The A to T transversion at the 61st codon of Ha-ras was heterozygous in all positive papillomas and carcinomas. No such mutation was found when benzo(a)pyrene was used as an initiating agent. These results indicate that fetal c-Ha-ras can be transplacentally activated through a specific point mutation by a carcinogen, but a cell harboring such a mutation may remain dormant until it encounters a tumor-promoting stimulus.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Comparison of regulations on occupational carcinogens in several industrialized countries.

Regulations controlling the manufacture and use of carcinogens in the industrial setting of various countries are examined. In addition, the occupational exposure limits (OEL) of chemicals known or suspected to be carcinogenic in humans are listed, and criteria for the establishment of OELs are discussed. It is also stressed that control measures should not be confined to a few developed countries, and it is hoped that attracting attention to their unevenness will contribute to the implementation of a more efficient primary prevention of cancer.

Carcinogens↗
PubMed1987

An efficient primary prevention of cancer requires an integrated approach: Mühlbock memorial lecture.

In addition to a wide gradation of levels of exposure to man-made, naturally occurring and endogenous chemicals, to viruses and to radiation, there is a gradation of genetic susceptibility for resistance to the mutagenic and other damaging effects of noxious environmental and endogenous agents. This interplay between environmental and host factors is probably not limited to the early stage of carcinogenesis but extends over the later stages of promotion and progression. The risk of cancer in humans is thus increased by a wide spectrum of factors, which ranges from exposure to an identified agent, such as environmental chemicals or a virus, to culturally determined behaviour, such as age at first pregnancy. We are able today to intervene in some of these factors, while others affect risk by as yet undetermined pathways. Only progress in the understanding of the mechanisms by which these factors act can lead to specific means of cancer prevention. New developments in molecular biology do not invalidate ipso facto all that has been done before. While the new insights about certain aspects of the carcinogenesis process and the new techniques that have been developed in parallel demand that new approaches be explored and developed, there is little justification for downgrading long-term carcinogenicity tests, which provide proven, efficient warning about possible hazards to humans. Support for the maintenance of a programme for testing of environmental chemicals does not mean, however, that one can expect that all or even most of the agents that are carcinogenic to humans will be identified by traditional long-term testing in rodents. Basic and applied research, studies on the mechanisms of carcinogenesis and research on aetiology and prevention are neither opposite nor separate areas of scientific activity. They must be, and indeed are, closely interrelated. The understanding of certain stages of the carcinogenesis process is progressing side by side with the development of much more precise methods than ever existed before for monitoring low doses of exposure at the individual level. While this will be of very considerable help in the conduct of epidemiological investigations, it is clear that the efficacy of primary prevention will increase with, and indeed depend on, understanding of the mechanisms by which a factor or a series of factors contribute to the malignant transformation of cells and/or to their progression to clinical cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗
PubMed1987

Persistence of carcinogenic effect in intact progeny of mice treated transplacentally with 7,12-dimethylbenz[a]anthracene.

Pregnant SHR mice were treated once with 7,12-dimethylbenz[a]anthracene (DMBA) on days 17-19 of gestation. F1 and F2 descendants of these mice received multiple skin applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week for 24 weeks beginning at 12 weeks of age, or applications of solvent alone. The increase in the frequency of skin tumours in F1 and F2 descendants was reported elsewhere. In addition, we report here an increase in overall numbers of tumor-bearing animals, independently of TPA treatment both in F1 and F2 groups compared to respective control groups. Separate statistical analyses were performed for lung tumours, mammary gland tumours, leukaemias and lymphomas. In both generations of descendants of DMBA-treated mothers lung tumour incidence was considerably increased and differed significantly (maximal P-value = 0.003) from control values. Local applications of TPA resulting in strong skin tumour promoting effect described in our previous paper (Napalkov et al., Carcinogenesis, 8(3) (1987) 381) did not produce any significant change in the rates of other types of tumours. The results of the present study provide additional evidence in support of the hypothesis on possibility of hereditary transmission of carcinogenic action of certain chemical compounds.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Promotion of skin tumours by TPA in the progeny of mice exposed pre-natally to DMBA.

Pregnant SHR mice were treated once with 7,12-dimethylbenz[a]anthracene (DMBA) on day 17-19 of gestation, and F1 and F2 descendants received multiple skin applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week for 24 weeks beginning at 12 weeks of age. Post-natal promoter treatment resulted in a high incidence of skin tumours in F1 and F2 mice (37.3 and 19.7%, respectively), whereas only 6.6% of control animals treated with TPA only developed skin tumours. DMBA was shown previously to be capable of initiating skin carcinogenesis transplacentally; however, our results on the second generation provide suggestive evidence of hereditary transmission of at least part of the initiating action of this carcinogen.

9,10-Dimethyl-1,2-benzanthracene↗