The induction of lung tumours by the injection of 9,10-dimethyl-1,2-benzanthracene (DMBA) into newborn suckling and young adult mice. A dose response study.

Abstract

A VARIETY of neoplasms has been induced by the injection of polycyclic hydrocarbons, urethane, alkylating agents and nitrosamines into newborni mice (Pietra, Spencer and Shubik, 1959;Pietra, Rappaport and Shubik. 1961 FioreDonati, Chieco-Bianchi, de Benedictis and Maiorano, 1961;Roe. Mitchley and Walters, 1963;Toth, Magee and Shubik, 1964). The experiments to be described were designed to investigate the sensitivity of newborn mice with a viewN to using the technique for screening compounds for carcinogenic activity. A range of doses of DMBA has been tested for activity in newborn mice, and the sensitivity of the newborn to the induction of lung tumours has been coinpared witlh that of sucklings and young adults. MATERIALS AND METHODSChemical agents.-9,10-Dimethyl-1,2-benzanthracene (DMBA) was obtained from Roche Products Ltd. and gelatine powder from British Drug Houses. A suspension of DMBA in 300 aqueous gelatine was prepared by adding an acetone solution of the compound to aqueous gelatine warmed to 560 C. The acetone was driven off in a stream of nitrogen while the temperature was maintainied at this level. The dose of DMBA administered to each mouse was cointainied in 002 ml. aqueous gelatine.Mice.-BALB 'c (Bittner agent free) mice were used in both experiments.The line was originally obtained from Dr. H. B. Andervont of the National Cancer Institute, Bethesda, Maryland, and has been maintained in this Institute by brother-sister mating since 1952. The mice were housed in metal cages and given water and fed a cubed diet (Diet 86, Messrs. Dixon and Sons, Ware, Herts.) ad libitum. Every mouse was vaccinated at 6 to S weeks of age as a precaution against ectromelia. Suckling and young adult mice were injected subcutaneously in the flank and newborn mice in the scapular region. In the case of the newborn, the needle was inserted at the root of the tail and the material was deposited in the scapular region to minimise leakage. Losses due to cannibalism by the mother were small. The mice were weaned at 4 weeks, numbered on the ears and housed. 4-6 to a cage, according to group and sex. They were inspected every day. and examined thoroughly once a week, and sick mice were killed and autopsied. All surviving mice were killed 40 weeks after the day of injection and examined post mortem.

DNA Damage from Polycyclic Aromatic Hydrocarbons Measured by Benzo[a]pyrene-DNA Adducts in Mothers and Newborns from Northern Manhattan, The World Trade Center Area, Poland, and China

“…Some PAHs are transplacental carcinogens in experimental bioassays, producing tumors in the liver, lung, lymphatic tissues, and nervous system of the offspring (4)(5)(6). Experimental animal studies have shown greater susceptibility to PAH-induced carcinogenesis when exposure occurs during the fetal and infancy periods than during adulthood (5)(6)(7)(8)(9). No comparable human data are available on age-related susceptibility to PAH carcinogenesis (10).…”

Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development

“…A synthetic PAH, DMBA (7,12-dimethylbenz[a]anthracene) has been used extensively to induce breast tumors in rodent models, and this model is used as the 'gold standard' to evaluate potential therapeutic modalities (Mehta, 2000). This carcinogen also induces tumors in rodents in other organs, when administered during juvenile development, principally for lung, liver and the hematopoietic lineages (Walters, 1966;Flaks, 1968;Roe and Walters, 1968;Akamatsu, 1975;Heidel et al, 2000).…”

Prenatal Smoking Exposure and Neonatal DNA Damage in Relation to Birth Outcomes

“…These compounds can cross the placenta and experimental animal studies have indicated that the fetus and newborn are more susceptible to carcinogens than adults (17)(18)(19). A study of white population showed that there is an increased susceptibility to DNA damage from PAHs and the diminished ability to clear ETS components for the fetus (20).…”