Neoplastic and Nonneoplastic Lesions in Aging (C57BL/6N × C3H/HeN)F1 (B6C3F1) Mice2

Ward, J. M.; Goodman, Dawn G.; Squire, Robert A.; Chu, Kenneth C.; Linhart, M.S.

doi:10.1093/jnci/63.3.849

Cited by 235 publications

(66 citation statements)

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“…Most malignant lymphomas seemed to originate in the thymus, which is different from spontaneous lymphomas observed in this strain of mouse (10). The thymus was the most frequently and prominently affected organ and occasionally the only affected organ.…”

Section: Malignant Lymphomacontrasting

confidence: 63%

Morphology of Neoplastic Lesions Induced by 1,3-Butadiene in B6C3F 1 Mice

Miller¹,

Boorman²

1990

Environmental Health Perspectives

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1,3-Butadiene (CAS No. 106-99-0) was studied for potential carcinogenicity and chronic toxicity by inhalation in B6C3Fj mice. Groups of 50 mice of each sex were exposed to 0, 625, or 1250 ppm 1,3-butadiene for 6 hr/day, 5 days/week for 60 weeks (male) or 61 weeks (female). The study was scheduled for 104 weeks of exposure but was terminated early because of reduced survival related to induction of a variety of tumors in 1,3-butadiene-exposed mice. A second chronic inhalation study was conducted in which male and female mice were exposed to 0, 6.25, 20, 62.5, 200, or 625 ppm for up to 2 years. Additional groups of50 male mice were exposed to 625 ppm for 13 or 26 weeks, 312 ppm for 52 weeks, or 200 ppm for 40 weeks, then held without exposure until scheduled sacrifice 104 weeks after initial exposure.1,3-Butadiene-exposed mice from both studies had increased incidences of malignant lymphomas that were observed as early as week 20 in the first study and week 23 in the second study. The lymphomas were primarily lymphocytic and originated in the thymus, although generalized lymphoma was often present.Exposed mice in both studies developed cardiac hemangiosarcomas that were observed as early as week 32 in the first study and week 41 in the second study. Also present were foci of endothelial hyperplasia in the myocardium that were regarded as early evidence of developing hemangiosarcoma. Alveolar epithelial hyperplasia, alveolar/bronchiolar adenomas and alveolar/bronchiolar carcinomas represented the spectrum of proliferative lung lesions induced by exposure to 1,3-butadiene in both studies. Exposure-related proliferative forestomach lesions observed in both studies included epithelial hyperplasia, squamous cell papillomas, and squamous cell carcinomas. 1,3-Butadiene-exposed female mice in both studies developed mammary gland neoplasms at increased incidences. Most of the mammary tumors were pleomorphic adenocarcinomas, but several adenoacanthomas were also seen. Granulosa cell tumors of the ovary were exposure-related neoplasms in both studies. Occasionally the granulosa cell tumors were malignant as evidenced by vascular invasion or pulmonary metastasis. Although there was an increased incidence of hepatocellular neoplasms in exposed females in the first study, by week 65 of the second study there was not evidence of a clear response of liver neoplasms. The preliminary results of the second study indicate there was induction of tumors similar to those seen in the first study but occurring in response to lower concentrations of 1,3-butadiene.

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Section: Malignant Lymphomacontrasting

confidence: 63%

Morphology of Neoplastic Lesions Induced by 1,3-Butadiene in B6C3F 1 Mice

Miller¹,

Boorman²

1990

Environmental Health Perspectives

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“…4,26,29 Enamel organ dysplasia, noted in most of the older mice, was previously recognized22 as a lesion that could lead to severe malformation of the teeth and subsequent death by inanition in old mice, but this lesion has been commonly overlooked in previous studies.…”

Section: Aging and Disease In Genetically Heterogeneous Micementioning

confidence: 99%

Lifespan and Lesions in Genetically Heterogeneous (Four-way Cross) Mice: A New Model for Aging Research

et al. 1996

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Abstract. Genetically heterogeneous animal models provide many advantages for research on aging but have been used infrequently. We present here lifespan and lesion data from a study of mice bred as a cross between (AKR/J x DBA/2J)F, females and (C57BL/6J x SJL/J)F, males. In such a four-way cross population, each mouse is genetically unique, but replicate populations of essentially similar genetic structure can be generated quickly, at low cost, and of arbitrary size from commercially available, genetically stable hybrid parents. We employed a protocol in which mice judged to be severely ill were euthanatized to obtain tissue in optimal condition for necropsy, and we were able to infer a likely cause of illness in 42 of 44 animals. Malignant lymphoma, including at least four histopathologically distinct subtypes, was the most common cause and was also a frequent incidental finding in mice dying of other causes. Neoplastic disease, benign or malignant, was the sole or a contributing cause of illness in 90% of the mice for which a cause could plausibly be assigned. A wide range of lethal and nonlethal degenerative lesions was also noted. The coefficient of variation for lifespan in these genetically heterogeneous mice was 26%, similar to that seen in analyses of recombinant inbred mouse lines. Baseline lifespan and pathology data on four-way cross mice is a useful prelude to the exploitation of this rodent model in tests of genetic and mechanistic hypotheses about aging.

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“…This model resembles those using chemical carcinogens to induce liver tumors in rats and choline deficiency and/or partial hepatectomy to enhance tumor development (19,31). Regarding the B(;C3F 1 mouse, it is worth pointing out that the appearance of the "spontaneous" liver nodules usually occur in animals older than one year (32) and that promoting conditions, such as CD diet, lowers that age to 6 months when the diet has been fed from weaning. These observations are even more impressive when one considers the putative pre-neoplastic hyperplastic foci that appear after 3 months on CD diet (17).…”

Section: Table L-composition Of Dietsmentioning

confidence: 99%

Choline Deficiency, Partial Hepatectomy, and Liver Tumors in Rats and Mice

1982

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Choline deficiency (CD) increases susceptability of the rat liver to a number of~epatocellular carcinogens with a wide diversity of structure and potency. While severe CD results in micronodular cirrhosis and enhanced tumor induction, even a mild deficiency, without cirrhosis is sufficient to result in the increased carcinogenic response. The effects of CD are in part mediated via modulation of microsomal and, possibly, cytosolic enzymes responsible for activation/deactivation of carcinogens.. The 86C3F1 hybrid mouse is remarkably sensitive to initiation/promotion of liver tumors by many substances or conditions. Choline deficiency or partial hepatectomy alone, or in concert, markedly enhances liver tumor induction in the absence of any known carcinogen. These data indicate that the liver of this strain of mouse is "initiated" at or shortly after birth and can be promoted by non-carcinogenic substances or conditions.

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Neoplastic and Nonneoplastic Lesions in Aging (C57BL/6N × C3H/HeN)F1 (B6C3F1) Mice2

Cited by 235 publications

References 0 publications

Morphology of Neoplastic Lesions Induced by 1,3-Butadiene in B6C3F 1 Mice

Morphology of Neoplastic Lesions Induced by 1,3-Butadiene in B6C3F 1 Mice

Lifespan and Lesions in Genetically Heterogeneous (Four-way Cross) Mice: A New Model for Aging Research

Choline Deficiency, Partial Hepatectomy, and Liver Tumors in Rats and Mice

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