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A J Ingram

Publications and source records attributed to A J Ingram.

6 recordsLinked to original sources
PubMed1992

Review of chemical and UV light-induced melanomas in experimental animals in relation to human melanoma incidence.

In a few epidemiological studies on oil refinery workers, a slight excess of melanoma incidence has been reported. To see if this might be linked to exposure to polycyclic aromatic hydrocarbons (PAHs) contained in refinery streams, a review of animal data on the relationship between PAH exposure, UV light and melanoma induction has been carried out and compared with human data. This revealed that the highly carcinogenic PAH 7,12-dimethylbenz[a]anthracene (DMBA) was capable of inducing melanomas in hamsters, mice and guinea pigs, but only under certain experimental conditions. Evidence suggested that other carcinogenic PAHs were unable to induce melanomas. As high dose levels of DMBA were generally required to produce melanomas, it was not considered that the amounts present in refinery streams would be sufficient to account for an increase in melanoma incidence in exposed workers. This conclusion was substantiated by the failure of petroleum-derived complex hydrocarbon mixtures to produce melanomas in animals or man and by drawing attention to the absence of any association between melanoma incidence and the incidence of other skin cancers in man. If PAHs were responsible for an increase in melanoma incidence, an increase in other skin tumours would also be expected. It was concluded that animal data, taken in conjunction with other information, do not suggest that PAH exposure is likely to be the cause of any elevation in melanoma incidence in refinery workers. More detailed epidemiological findings would be required to establish whether any excess incidence of melanomas was due to sunlight, other risk factors or chance occurrences.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Evidence for and possible mechanisms of non-genotoxic carcinogenesis in mouse skin.

Most chemicals that produce skin cancer are genotoxic by in vitro and in vivo short-term assays and produce a high incidence of skin cancer within a year if optimal doses are applied. If in long-term skin painting studies one or two tumours in 50 mice are observed there is a general consensus that no carcinogenic activity can be claimed and it has been suggested that if up to 10% tumours are induced by irritant substances this could be due to an enhancement of spontaneous tumour incidence. Observations of skin tumour incidences higher than 10% with non-genotoxic substances, usually after a long latent period, is considered to represent evidence for a non-genotoxic mechanism. Examples of such substances include croton oil, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), sodium hydroxide, potassium hydroxide, phenol, dodecylbenzene and petroleum-derived middle distillates. Two distinct mechanisms appear to be involved in the production of tumours by a non-genotoxic substance. The first of these is that seen with the strong promoting agents. These, by binding to and activating protein kinase C, appear to directly stimulate sustained epidermal hyperplasia without severe skin damage. The other appears to involve substances producing severe skin damage either by a direct caustic effect or by cumulative irritancy. These changes give rise to marked epidermal hyperplasia with repeated episodes of regeneration and damage. The tumour induction by both mechanisms probably results from oncogene activation and it is possible that oxidative enzymes from inflammatory cells may be involved in the activation process. Various reasons are given why non-genotoxic carcinogenesis in the skin is considered not to be relevant to man and ways of recognising and avoiding its occurrence in animals studies are recommended.

Animals↗
PubMed1979

Interaction of benzo [A] pyrene and a hyperplastic agent in epidermal nuclear enlargement in the mouse. A dose response study.

Experiments were conducted on the effects of various dose levels of benzo [a]pyrene (BP) on nuclear size in mouse interfollicular epidermis over a 3-day period. Topical application of BP was made with or without croton oil (CO) (0.1 or 0.5%) in the vehicles acetone, toluene and methyl ethyl ketone (MEK). Nuclear size was measured on histological sections either manually or by Quantimet Image Analyser. Vehicle controls treated with 0.1 or 0.5% CO in acetone or MEK gave rise to epidermal hyperplasia with some nuclear enlargement and toluene without CO produced a similar response. It was found that when BP was applied in a vehicle capable of inducing hyperplasia, the nuclear enlargement produced was greater than that produced by either the vehicle control or BP in a non-irritant vehicle. The enhancement of response to BP when tested in the presence of a hyperplastic agent resulted in lower concentrations of BP being detectable. As the levels of BP detectable by nuclear enlargement under these conditions compared reasonably well with those detectable in long-term tests, this system might be usable as a basis for a short-term test for carcinogens.

Animals↗
PubMed1977

Nuclear enlargement and DNA synthesis in mouse epidermis treated with carcinogen and promotor.

An autoradiographic investigation was made into the causes of nuclear size increase observed in the mouse epidermis within a few days of topical benzpyrene treatment. The effects of croton oil pretreatment of posttreatment in combination with benzpyrene were examined to see what effect a growth stimulus had on this response. The degree of nuclear size increase induced in the epidermis suggested that some ploidy level increase resulted from combined croton oil and benzpyrene treatment and evidence was found of a G2 block occurring in association with this. Enhancement of nuclear size increase by croton oil highlighted the importance of a growth stimulus in carcinogen induced nuclear enlargement and the implications of this are discussed. Disappearance of enlarged nuclei was seen when mice were kept for 5 days after combined croton oil and benzpyrene treatment in spite of a reduced cell loss compared with croton oil treatment alone.

Animals↗
PubMed1975

Patch testing in the rabbit using a modified human patch test method. Application of histological and visual assessement.

A 5 h, semi-occlusive human patch test repeated daily for 5 days, was modified for use in the rabbit Using this method, the relative irritancy of three cosmetic samples of known human irritancy was determined in the rabbit. In addition, attention was paid to assessment methods and a detailed histological scoring system is described as well as two methods of visual assessment. In order to compare the effectiveness of these methods, the reaction to a series of concentrations of sodium lauryl sulphate was examined. All three assessment methods gave similar results and the merits of combining histological and visual assessment are discussed.

Acanthosis Nigricans↗