Critical Significance of Breast Structure in the Induction of Mammary Cancer in the Rat

Huggins, Charles; Grand, Lorraine C.; Brillantes, Filomena P.

doi:10.1073/pnas.45.8.1294

Cited by 63 publications

(30 citation statements)

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“…The age of the animal at the start of treatment had some bearing on tumour yield and induction time, since using older animals, the tumour incidence fell, and the average induction time increased. Employing the same technique but with rats of 42 days old and increasing the daily dose of methylcholanthrene to 10 mg., Huggins, Briziarelli and Sutton (1959) months, whereas using a 1.6 per cent solution, the average induction time fell to 4.75 months although the tumour incidence was unaltered (Howell, 1959 (Huggins, Grand and Brillantes, 1959).…”

Section: Discussionmentioning

confidence: 99%

“…growth hormone (Moon et al, 1950) and oestrogens (Geschickter, 1939; Mackenzie, 1955), by the administration of aminofluorene compounds (Bielschowsky, 1944(Bielschowsky, , 1947 Symeonidis, 1954) and by certain carcinogenic hydrocarbons. These latter substances have been administered by various routes, but the most rapid method of induction has been reported by Huggins, Briziarelli and Sutton (1959) giving methylcholanthrene daily by stomach tube, a technique originally described by Shay et al (1949).Painting the skin of the rat with an oily solution of 9: 10-dimethyl-1: 2-benzanthracene (DMB) at fortnightly intervals is a highly effective method of inducing breast tumours. In initial experiments (Howell, 1959) it was shown that 77 per cent of female rats developed mammary tumours in an average time of 4-75 months, and furthermore, a single application of the carcinogen gave a tumour incidence of 75 per cent, although in this instance the average induction time was extended to 12 months.…”

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The Chemical Induction of Breast Tumours in the Rat: Hormonal Factors in Tumour Production

Howell

1960

Br J Cancer

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MAMMARY tumours in the rat can be induced by a variety of methods. These include intensive treatment with hormone preparations, e.g. growth hormone (Moon et al., 1950) and oestrogens (Geschickter, 1939; Mackenzie, 1955), by the administration of aminofluorene compounds (Bielschowsky, 1944(Bielschowsky, , 1947 Symeonidis, 1954) and by certain carcinogenic hydrocarbons. These latter substances have been administered by various routes, but the most rapid method of induction has been reported by Huggins, Briziarelli and Sutton (1959) giving methylcholanthrene daily by stomach tube, a technique originally described by Shay et al. (1949).Painting the skin of the rat with an oily solution of 9: 10-dimethyl-1: 2-benzanthracene (DMB) at fortnightly intervals is a highly effective method of inducing breast tumours. In initial experiments (Howell, 1959) it was shown that 77 per cent of female rats developed mammary tumours in an average time of 4-75 months, and furthermore, a single application of the carcinogen gave a tumour incidence of 75 per cent, although in this instance the average induction time was extended to 12 months. The present paper is concerned with the effects of gonadectomy, hormone supplements and the effects of normal and pathological lactation on tumour development following skin application of DMB. The experiments on lactation were undertaken since Marchant (1958) has shown that breast tumour development in IF mice is inhibited by full lactation, and that unilateral removal of the nipples in lactating IF mice allows the development of breast tumours on the side without nipples, but not on the normal side (Marchant, 1959). MATERIALS AND METHODS GeneralThe animals were derived from two sources; entirely outbred laboratory stock, and from the Birmingham strain (Laboratory Animals Bureau Catalogue of Uniform Strains, No. 626, 1953).In all experiments, the animals whose age at the start of carcinogenic treatment varied between 2 and 4 months were kept in galvanized wire-mesh cages, never more than 5 rats to a cage, and were given rat cube (Heygate & Sons, known as the Thompson diet) and water ad lib. Twenty drops of a 1.6 per cent solution of DMB in olive oil was applied to the skin at fortnightly intervals, 5 drops to each side of the ventral and dorsal surfaces; a single treatment averaged 1.3 ml. or 20.8 mg.DMB. After the first month of treatment all the animals were examined at fortnightly intervals to determine the presence of palpable breast tumours. When a tumour was found, treatment. was stopped and usually the animal was killed,

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Section: Discussionmentioning

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The Chemical Induction of Breast Tumours in the Rat: Hormonal Factors in Tumour Production

Howell

1960

Br J Cancer

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“…Several studies (29)(30)(31) have addressed the association between cancer in humans and agricultural pesticide exposure, both occupational (e.g., farmers) and non-occupational, exposed to contaminated clothing, soil, ground and surface water, as well as drifts from aerial spraying of pesticides. It has been demonstrated that mammary carcinoma formation in Sprague-Dawley rats can be induced by chemical carcinogens (32)(33)(34)(35)(36). Dimethylbenz[α]anthracene (DMBA) induced mammary carcinomas in 100% of the animals with a latency period of 86 days (32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Catechol estrogens as biomarkers for mammary gland cancer

Calaf

2011

Int J Oncol

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Abstract. The origin of human tumors has been attributed to the exposure to several environmental chemicals and implicated in the increase of incidence in breast cancer. Progression of breast cancer follows a complex multistep process that seems to depend on various exogenous and endogenous factors. The aim of this study was to examine the effects of the organophosphorous pesticide malathion in the presence of estrogen on neoplastic transformation of rat mammary glands. Virgin female rats were sacrificed after 30, 124 and 240 days of 5-day injections twice a day. There were four groups: i) control, ii) malathion (22 mg/100 g body weight, BW), iii) 17β-estradiol (30 µg/100 g BW) and iv) combination of both. Progressive alterations in ducts were observed by the effect of malathion in comparison to control after 240 days. Ducts markedly increased in size and number of cells per square millimeter and tumors similar to ductal carcinoma were originated. The increase in number of proliferative ducts per square millimeter was significantly (P<0.05) higher in malathion-treated animals compared to the other groups. Progressive alterations in lobules with estrogen treatment were found after 240 days. Lobules became markedly abnormal, referred to as secretory lobules, increased in number and size and the tumors originated were similar to lobular carcinoma. The increase in number of secretory lobules was significantly (P<0.05) higher in estrogentreated animals compared to the other groups. Treatment with the combination of malathion and estrogen gave rise to tumors constituted of both proliferative ducts and secretory lobules as well as formation of estrogen metabolites such as 2 and 4 catechol estrogens in the blood of the animals after 240 days. We concluded that morphological changes and alterations in the blood of the animals can be used as biomarkers for mammary gland cancer.

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“…Myc is an absolute requirement for the efficient proliferation of normal as well as cancer cells (Evan, 2012). Modern studies of experimentally induced chemical carcinogenesis began with the introduction of polynuclear hydrocarbons such as 3-methyl chloranthracene (MCA), 7, 12-dimethyl benzanthracene (DMBA) (Huggins et al, 1959) and MNU (Gullino et al, 1975) as chemical carcinogens. Tumours induced in rats by administration of chemical carcinogens such as 7,12-dimethylbenzanthracene(DMBA) (Russo and Russo, 2000) and N-methyl nitrosourea constitute useful tools for dissecting the multistep carcinogenesis, which involves initiation, promotion, and progression.…”

Section: Introductionmentioning

confidence: 99%

Upregulated Myc Expression in N-Methyl Nitrosourea (MNU)-induced Rat Mammary Tumours

Barathidasan

Pawaiya²,

Bahal³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Critical Significance of Breast Structure in the Induction of Mammary Cancer in the Rat

Cited by 63 publications

References 4 publications

The Chemical Induction of Breast Tumours in the Rat: Hormonal Factors in Tumour Production

The Chemical Induction of Breast Tumours in the Rat: Hormonal Factors in Tumour Production

Catechol estrogens as biomarkers for mammary gland cancer

Upregulated Myc Expression in N-Methyl Nitrosourea (MNU)-induced Rat Mammary Tumours

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